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1
Ciocanel, Maria-Veronica, Aravind Chandrasekaran, Carli Mager, Qin Ni, Garegin A. Papoian, and Adriana Dawes. "Simulated actin reorganization mediated by motor proteins." PLOS Computational Biology 18, no. 4 (2022): e1010026. http://dx.doi.org/10.1371/journal.pcbi.1010026.
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Cortical actin networks are highly dynamic and play critical roles in shaping the mechanical properties of cells. The actin cytoskeleton undergoes significant reorganization in many different contexts, including during directed cell migration and over the course of the cell cycle, when cortical actin can transition between different configurations such as open patched meshworks, homogeneous distributions, and aligned bundles. Several types of myosin motor proteins, characterized by different kinetic parameters, have been involved in this reorganization of actin filaments. Given the limitations in studying the interactions of actin with myosin in vivo, we propose stochastic agent-based models and develop a set of data analysis measures to assess how myosin motor proteins mediate various actin organizations. In particular, we identify individual motor parameters, such as motor binding rate and step size, that generate actin networks with different levels of contractility and different patterns of myosin motor localization, which have previously been observed experimentally. In simulations where two motor populations with distinct kinetic parameters interact with the same actin network, we find that motors may act in a complementary way, by tuning the actin network organization, or in an antagonistic way, where one motor emerges as dominant. This modeling and data analysis framework also uncovers parameter regimes where spatial segregation between motor populations is achieved. By allowing for changes in kinetic rates during the actin-myosin dynamic simulations, our work suggests that certain actin-myosin organizations may require additional regulation beyond mediation by motor proteins in order to reconfigure the cytoskeleton network on experimentally-observed timescales.
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Brown, Susan S. "Cooperation Between Microtubule- and Actin-Based Motor Proteins." Annual Review of Cell and Developmental Biology 15, no. 1 (1999): 63–80. http://dx.doi.org/10.1146/annurev.cellbio.15.1.63.
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Wolgemuth, Charles W., and Sean X. Sun. "Active random forces can drive differential cellular positioning and enhance motor-driven transport." Molecular Biology of the Cell 31, no. 20 (2020): 2283–88. http://dx.doi.org/10.1091/mbc.e19-11-0629.
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Chabrillat, Marion L., Claire Wilhelm, Christina Wasmeier, Elena V. Sviderskaya, Daniel Louvard, and Evelyne Coudrier. "Rab8 Regulates the Actin-based Movement of Melanosomes." Molecular Biology of the Cell 16, no. 4 (2005): 1640–50. http://dx.doi.org/10.1091/mbc.e04-09-0770.
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Rab GTPases have been implicated in the regulation of specific microtubule- and actin-based motor proteins. We devised an in vitro motility assay reconstituting the movement of melanosomes on actin bundles in the presence of ATP to investigate the role of Rab proteins in the actin-dependent movement of melanosomes. Using this assay, we confirmed that Rab27 is required for the actin-dependent movement of melanosomes, and we showed that a second Rab protein, Rab8, also regulates this movement. Rab8 was partially associated with mature melanosomes. Expression of Rab8Q67L perturbed the cellular distribution and increased the frequency of microtubule-independent movement of melanosomes in vivo. Furthermore, anti-Rab8 antibodies decreased the number of melanosomes moving in vitro on actin bundles, whereas melanosomes isolated from cells expressing Rab8Q67L exhibited 70% more movements than wild-type melanosomes. Together, our observations suggest that Rab8 is involved in regulating the actin-dependent movement of melanosomes.
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Titus, M. A., H. M. Warrick, and J. A. Spudich. "Multiple actin-based motor genes in Dictyostelium." Cell Regulation 1, no. 1 (1989): 55–63. http://dx.doi.org/10.1091/mbc.1.1.55.
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Dictyostelium cells, devoid of conventional myosin, display a variety of motile activities, consistent with the presence of other molecular motors. The Dictyostelium genome was probed at low stringency with a gene fragment containing the conserved conventional myosin head domain sequences to identify other actin-based motors that may play a role in the observed motility of these mutant cells. One gene (abmA) has been characterized and encodes a polypeptide of approximately 135 kDa with a head region homologous to other myosin head sequences and a tail region that is not predicted to form either an alpha-helical structure of coiled-coil interactions. Comparisons of the amino acid sequences of the tail regions of abmA, Dictyostelium myosin I, and Acanthamoeba myosins IB and IL reveal an area of sequence similarity in the amino terminal half of the tail that may be a membrane-binding domain. The abmA gene, however, does not contain an unusual Gly, Pro, Ala stretch typical of many of the previously described myosin Is. Two additional genes (abmB and abmC) were identified using this approach and also found to contain sequences that encode proteins with typical conserved myosin head sequences. The abm genes may be part of a large family of actin-based motors that play various roles in diverse aspects of cellular motility.
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Koonce, Michael P. "13 Plus 1: A 30-Year Perspective on Microtubule-Based Motility in Dictyostelium." Cells 9, no. 3 (2020): 528. http://dx.doi.org/10.3390/cells9030528.
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Individual gene analyses of microtubule-based motor proteins in Dictyostelium discoideum have provided a rough draft of its machinery for cytoplasmic organization and division. This review collates their activities and looks forward to what is next. A comprehensive approach that considers the collective actions of motors, how they balance rates and directions, and how they integrate with the actin cytoskeleton will be necessary for a complete understanding of cellular dynamics.
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Kumpula, Esa-Pekka, and Inari Kursula. "Towards a molecular understanding of the apicomplexan actin motor: on a road to novel targets for malaria remedies?" Acta Crystallographica Section F Structural Biology Communications 71, no. 5 (2015): 500–513. http://dx.doi.org/10.1107/s2053230x1500391x.
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Apicomplexan parasites are the causative agents of notorious human and animal diseases that give rise to considerable human suffering and economic losses worldwide. The most prominent parasites of this phylum are the malaria-causingPlasmodiumspecies, which are widespread in tropical and subtropical regions, andToxoplasma gondii, which infects one third of the world's population. These parasites share a common form of gliding motility which relies on an actin–myosin motor. The components of this motor and the actin-regulatory proteins in Apicomplexa have unique features compared with all other eukaryotes. This, together with the crucial roles of these proteins, makes them attractive targets for structure-based drug design. In recent years, several structures of glideosome components, in particular of actins and actin regulators from apicomplexan parasites, have been determined, which will hopefully soon allow the creation of a complete molecular picture of the parasite actin–myosin motor and its regulatory machinery. Here, current knowledge of the function of this motor is reviewed from a structural perspective.
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Müller, Kei W., Anna M. Birzle, and Wolfgang A. Wall. "Beam finite-element model of a molecular motor for the simulation of active fibre networks." Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences 472, no. 2185 (2016): 20150555. http://dx.doi.org/10.1098/rspa.2015.0555.
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Molecular motors are proteins that excessively increase the efficiency of subcellular transport processes. They allow for cell division, nutrient transport and even macroscopic muscle movement. In order to understand the effect of motors in large biopolymer networks, e.g. the cytoskeleton, we require a suitable model of a molecular motor. In this contribution, we present such a model based on a geometrically exact beam finite-element formulation. We discuss the numerical model of a non-processive motor such as myosin II, which interacts with actin filaments. Based on experimental data and inspired by the theoretical understanding offered by the power-stroke model and the swinging-cross-bridge model, we parametrize our numerical model in order to achieve the effect that a physiological motor has on its cargo. To this end, we introduce the mechanical and mathematical foundations of the model, then discuss its calibration, prove its usefulness by conducting finite-element simulations of actin–myosin motility assays and assess the influence of motors on the rheology of semi-flexible biopolymer networks.
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Vandenboom, Rene. "The Myofibrillar Complex and Fatigue: A Review." Canadian Journal of Applied Physiology 29, no. 3 (2004): 330–56. http://dx.doi.org/10.1139/h04-022.
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The basis for all biological movement is the conversion of chemical energy to mechanical energy by different classes of motor proteins. In skeletal muscle this motor protein is myosin II, a thick filament-based molecule that harnesses the free energy furnished by ATP hydrolysis to perform mechanical work against actin proteins of the thin filament. The cyclic attachment and detachment of myosin with actin that generates muscle force and shortening is Ca2+ regulated. Intense muscle activity may lead to metabolically induced inhibitions to the function of these myofibrillar proteins when Ca2+ regulation is normal, a phenomenon referred to as myofibrillar fatigue. Studies using single muscle fibers at room temperature or lower have shown that myosin motor function is inhibited by the accumulation of the ATP-hydrolysis products ADP, Pi, and H+ as well as by excess generation of reactive oxygen species (ROS). These metabolically induced impairments to myosin motor function reduce muscle work and power output by impairing maximal Ca2+ activated force, the Ca2+ sensitivity of force, and/or unloaded shortening velocity. Based on uncertainties about their inhibitory effect on muscle function at more physiological temperatures, the influence of ATP-hydrolysis product and ROS accumulation on myofibrillar protein function of human skeletal muscle remains to be clarified. Key words: actin, myosin, muscle contraction
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McQuarrie, Irvine G., and Linda M. Lund. "INTRA-AXONAL MYOSIN AND ACTIN IN NERVE REGENERATION." Neurosurgery 65, suppl_4 (2009): A93—A96. http://dx.doi.org/10.1227/01.neu.0000338593.76635.32.
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Abstract A FOCUSED REVIEW of sciatic nerve regeneration in the rat model, based on research conducted by the authors, is presented. We examine structural proteins carried distally in the axon by energy-requiring motor enzymes, using protein chemistry and molecular biology techniques in combination with immunohistochemistry. Relevant findings from other laboratories are cited and discussed. The general conclusion is that relatively large amounts of actin and tubulin are required to construct a regenerating axon and that these materials mainly originate in the parent axon. The motor enzymes that carry these proteins forward as macromolecules include kinesin and dynein but probably also include myosin.
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Evans, L. L., A. J. Lee, P. C. Bridgman, and M. S. Mooseker. "Vesicle-associated brain myosin-V can be activated to catalyze actin-based transport." Journal of Cell Science 111, no. 14 (1998): 2055–66. http://dx.doi.org/10.1242/jcs.111.14.2055.
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Myosin-V has been linked to actin-based organelle transport by a variety of genetic, biochemical and localization studies. However, it has yet to be determined whether myosin-V functions as an organelle motor. To further investigate this possibility, we conducted a biochemical and functional analysis of organelle-associated brain myosin-V. Using the initial fractionation steps of an established protocol for the purification of brain myosin-V, we isolated a population of brain microsomes that is approx. fivefold enriched for myosin-V, and is similarly enriched for synaptic vesicle proteins. As demonstrated by immunoelectron microscopy, myosin-V associates with 30–40% of the vesicles in this population. Although a majority of myosin-V-associated vesicles also label with the synaptic vesicle marker protein, SV2, less than half of the total SV2-positive vesicles label with myosin-V. The average size of myosin-V/SV2 double-labeled vesicles (90+/−45 nm) is larger than vesicles that label only with SV2 antibodies (60+/−30 nm). To determine if these vesicles are capable of actin-based transport, we used an in vitro actin filament motility assay in which vesicles were adsorbed to motility assay substrates. As isolated, the myosin-V-associated vesicle fraction was nonmotile. However, vesicles pre-treated with ice-cold 0.1% Triton X-100 supported actin filament motility at rates comparable to those on purified myosin-V. This dilute detergent treatment did not disrupt vesicle integrity. Furthermore, while this treatment removed over 80% of the total vesicle proteins, myosin-V remained tightly vesicle-associated. Finally, function-blocking antibodies against the myosin-V motor domain completely inhibited motility on these substrates. These studies provide direct evidence that vesicle-associated myosin-V is capable of actin transport, and suggest that the activity of myosin-V may be regulated by proteins or lipids on the vesicle surface.
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Wu, Hao, Jing Zhou, Tianhui Zhu, Ivan Cohen, and Jason Dictenberg. "A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice." Journal of Biological Chemistry 295, no. 19 (2020): 6605–28. http://dx.doi.org/10.1074/jbc.ra118.005616.
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Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse primary hippocampal neuronal cultures from both sexes and using structured illumination microscopic imaging of these neurons, we observed that brain-derived neurotrophic factor (BDNF) enhances co-localization of dendritic ZBP1 and PAT1 within granules that also contain kinesin-I. PAT1 is essential for BDNF-stimulated neuronal growth cone development and dendritic protrusion formation, and we noted that ZBP1 and PAT1 co-locate along with β-actin mRNA in actively transported granules in living neurons. Acute disruption of the PAT1–ZBP1 interaction in neurons with PAT1 siRNA or a dominant-negative ZBP1 construct diminished localization of β-actin mRNA but not of Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) mRNA in dendrites. The aberrant β-actin mRNA localization resulted in abnormal dendritic protrusions and growth cone dynamics. These results suggest a critical role for PAT1 in BDNF-induced β-actin mRNA transport during postnatal development and reveal a new molecular mechanism for mRNA localization in vertebrates.
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Goodson, H. V., B. L. Anderson, H. M. Warrick, L. A. Pon, and J. A. Spudich. "Synthetic lethality screen identifies a novel yeast myosin I gene (MYO5): myosin I proteins are required for polarization of the actin cytoskeleton." Journal of Cell Biology 133, no. 6 (1996): 1277–91. http://dx.doi.org/10.1083/jcb.133.6.1277.
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The organization of the actin cytoskeleton plays a critical role in cell physiology in motile and nonmotile organisms. Nonetheless, the function of the actin based motor molecules, members of the myosin superfamily, is not well understood. Deletion of MYO3, a yeast gene encoding a "classic" myosin I, has no detectable phenotype. We used a synthetic lethality screen to uncover genes whose functions might overlap with those of MYO3 and identified a second yeast myosin 1 gene, MYO5. MYO5 shows 86 and 62% identity to MYO3 across the motor and non-motor regions. Both genes contain an amino terminal motor domain, a neck region containing two IQ motifs, and a tail domain consisting of a positively charged region, a proline-rich region containing sequences implicated in ATP-insensitive actin binding, and an SH3 domain. Although myo5 deletion mutants have no detectable phenotype, yeast strains deleted for both MYO3 and MYO5 have severe defects in growth and actin cytoskeletal organization. Double deletion mutants also display phenotypes associated with actin disorganization including accumulation of intracellular membranes and vesicles, cell rounding, random bud site selection, sensitivity to high osmotic strength, and low pH as well as defects in chitin and cell wall deposition, invertase secretion, and fluid phase endocytosis. Indirect immunofluorescence studies using epitope-tagged Myo5p indicate that Myo5p is localized at actin patches. These results indicate that MYO3 and MYO5 encode classical myosin I proteins with overlapping functions and suggest a role for Myo3p and Myo5p in organization of the actin cytoskeleton of Saccharomyces cerevisiae.
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Meinecke, Christoph R., Georg Heldt, Thomas Blaudeck, et al. "Nanolithographic Fabrication Technologies for Network-Based Biocomputation Devices." Materials 16, no. 3 (2023): 1046. http://dx.doi.org/10.3390/ma16031046.
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Network-based biocomputation (NBC) relies on accurate guiding of biological agents through nanofabricated channels produced by lithographic patterning techniques. Here, we report on the large-scale, wafer-level fabrication of optimized microfluidic channel networks (NBC networks) using electron-beam lithography as the central method. To confirm the functionality of these NBC networks, we solve an instance of a classical non-deterministic-polynomial-time complete (“NP-complete”) problem, the subset-sum problem. The propagation of cytoskeletal filaments, e.g., molecular motor-propelled microtubules or actin filaments, relies on a combination of physical and chemical guiding along the channels of an NBC network. Therefore, the nanofabricated channels have to fulfill specific requirements with respect to the biochemical treatment as well as the geometrical confienement, with walls surrounding the floors where functional molecular motors attach. We show how the material stack used for the NBC network can be optimized so that the motor-proteins attach themselves in functional form only to the floor of the channels. Further optimizations in the nanolithographic fabrication processes greatly improve the smoothness of the channel walls and floors, while optimizations in motor-protein expression and purification improve the activity of the motor proteins, and therefore, the motility of the filaments. Together, these optimizations provide us with the opportunity to increase the reliability of our NBC devices. In the future, we expect that these nanolithographic fabrication technologies will enable production of large-scale NBC networks intended to solve substantially larger combinatorial problems that are currently outside the capabilities of conventional software-based solvers.
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Balabanian, Linda, Abdullah R. Chaudhary, and Adam G. Hendricks. "Traffic control inside the cell: microtubule-based regulation of cargo transport." Biochemist 40, no. 2 (2018): 14–17. http://dx.doi.org/10.1042/bio04002014.
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The cell relies on an intricate system of molecular highways and motors to transport proteins, organelles and other vesicular cargoes to their proper locations. Microtubules, long filaments that form a network throughout the cell, act as highways. The motor proteins kinesin and dynein associate with cargoes and transport them along microtubules. Rather than simply acting as passive tracks, microtubules contain signals that regulate kinesin and dynein to target cargoes to specific locations in the cell. These signals include the organization of the microtubule network, chemical modifications that alter the microtubule surface properties and mechanics, and microtubuleassociated proteins that modulate the motility of motor proteins and microtubule polymerization.
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Phillips, J. C. "Self-organized networks: Darwinian evolution of dynein rings, stalks, and stalk heads." Proceedings of the National Academy of Sciences 117, no. 14 (2020): 7799–802. http://dx.doi.org/10.1073/pnas.1920840117.
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Cytoskeletons are self-organized networks based on polymerized proteins: actin, tubulin, and driven by motor proteins, such as myosin, kinesin, and dynein. Their positive Darwinian evolution enables them to approach optimized functionality (self-organized criticality). Dynein has three distinct titled subunits, but how these units connect to function as a molecular motor is mysterious. Dynein binds to tubulin through two coiled coil stalks and a stalk head. The energy used to alter the head binding and propel cargo along tubulin is supplied by ATP at a ring 1,500 amino acids away. Here, we show how many details of this extremely distant interaction are explained by water waves quantified by thermodynamic scaling. Water waves have shaped all proteins throughout positive Darwinian evolution, and many aspects of long-range water–protein interactions are universal (described by self-organized criticality). Dynein water waves resembling tsunami produce nearly optimal energy transport over 1,500 amino acids along dynein’s one-dimensional peptide backbone. More specifically, this paper identifies many similarities in the function and evolution of dynein compared to other cytoskeleton proteins such as actin, myosin, and tubulin.
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Kallio, Juha Pekka, and Inari Kursula. "Recombinant production, purification and crystallization of theToxoplasma gondiicoronin WD40 domain." Acta Crystallographica Section F Structural Biology Communications 70, no. 4 (2014): 517–21. http://dx.doi.org/10.1107/s2053230x14005196.
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Toxoplasma gondiiis one of the most widely spread parasitic organisms in the world. Together with other apicomplexan parasites, it utilizes a special actin–myosin motor for its cellular movement, called gliding motility. This actin-based process is regulated by a small set of actin-binding proteins, which in Apicomplexa comprises only 10–15 proteins, compared with >150 in higher eukaryotes. Coronin is a highly conserved regulator of the actin cytoskeleton, but its functions, especially in parasites, have remained enigmatic. Coronins consist of an N-terminal actin-binding β-propeller WD40 domain, followed by a conserved region, and a C-terminal coiled-coil domain implicated in oligomerization. Here, the WD40 domain and the conserved region of coronin fromT. gondiiwere produced recombinantly and crystallized. A single-wavelength diffraction data set was collected to a resolution of 1.65 Å. The crystal belonged to the orthorhombic space groupC2221, with unit-cell parametersa= 55.13,b= 82.51,c= 156.98 Å.
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Pertici, Irene, Giulio Bianchi, Lorenzo Bongini, Vincenzo Lombardi, and Pasquale Bianco. "A Myosin II-Based Nanomachine Devised for the Study of Ca2+-Dependent Mechanisms of Muscle Regulation." International Journal of Molecular Sciences 21, no. 19 (2020): 7372. http://dx.doi.org/10.3390/ijms21197372.
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The emergent properties of the array arrangement of the molecular motor myosin II in the sarcomere of the striated muscle, the generation of steady force and shortening, can be studied in vitro with a synthetic nanomachine made of an ensemble of eight heavy-meromyosin (HMM) fragments of myosin from rabbit psoas muscle, carried on a piezoelectric nanopositioner and brought to interact with a properly oriented actin filament attached via gelsolin (a Ca2+-regulated actin binding protein) to a bead trapped by dual laser optical tweezers. However, the application of the original version of the nanomachine to investigate the Ca2+-dependent regulation mechanisms of the other sarcomeric (regulatory or cytoskeleton) proteins, adding them one at a time, was prevented by the impossibility to preserve [Ca2+] as a free parameter. Here, the nanomachine is implemented by assembling the bead-attached actin filament with the Ca2+-insensitive gelsolin fragment TL40. The performance of the nanomachine is determined both in the absence and in the presence of Ca2+ (0.1 mM, the concentration required for actin attachment to the bead with gelsolin). The nanomachine exhibits a maximum power output of 5.4 aW, independently of [Ca2+], opening the possibility for future studies of the Ca2+-dependent function/dysfunction of regulatory and cytoskeletal proteins.
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Doran, Matthew H., and William Lehman. "The Central Role of the F-Actin Surface in Myosin Force Generation." Biology 10, no. 12 (2021): 1221. http://dx.doi.org/10.3390/biology10121221.
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Actin is one of the most abundant and versatile proteins in eukaryotic cells. As discussed in many contributions to this Special Issue, its transition from a monomeric G-actin to a filamentous F-actin form plays a critical role in a variety of cellular processes, including control of cell shape and cell motility. Once polymerized from G-actin, F-actin forms the central core of muscle-thin filaments and acts as molecular tracks for myosin-based motor activity. The ATP-dependent cross-bridge cycle of myosin attachment and detachment drives the sliding of myosin thick filaments past thin filaments in muscle and the translocation of cargo in somatic cells. The variation in actin function is dependent on the variation in muscle and non-muscle myosin isoform behavior as well as interactions with a plethora of additional actin-binding proteins. Extensive work has been devoted to defining the kinetics of actin-based force generation powered by the ATPase activity of myosin. In addition, over the past decade, cryo-electron microscopy has revealed the atomic-evel details of the binding of myosin isoforms on the F-actin surface. Most accounts of the structural interactions between myosin and actin are described from the perspective of the myosin molecule. Here, we discuss myosin-binding to actin as viewed from the actin surface. We then describe conserved structural features of actin required for the binding of all or most myosin isoforms while also noting specific interactions unique to myosin isoforms.
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Lee, Beth. "Myosins in Osteoclast Formation and Function." Biomolecules 8, no. 4 (2018): 157. http://dx.doi.org/10.3390/biom8040157.
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Skeletal quantity and quality are determined by processes of bone modeling and remodeling, which are undertaken by cells that build and resorb bone as they respond to mechanical, hormonal, and other external and internal signals. As the sole bone resorptive cell type, osteoclasts possess a remarkably dynamic actin cytoskeleton that drives their function in this enterprise. Actin rearrangements guide osteoclasts’ capacity for precursor fusion during differentiation, for migration across bone surfaces and sensing of their composition, and for generation of unique actin superstructures required for the resorptive process. In this regard, it is not surprising that myosins, the superfamily of actin-based motor proteins, play key roles in osteoclast physiology. This review briefly summarizes current knowledge of the osteoclast actin cytoskeleton and describes myosins’ roles in osteoclast differentiation, migration, and actin superstructure patterning.
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Vale, Ronald D., Ryan Case, Elena Sablin, Cindy Hart, and Robert Fletterick. "Searching for kinesin's mechanical amplifier." Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences 355, no. 1396 (2000): 449–57. http://dx.doi.org/10.1098/rstb.2000.0586.
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Kinesin, a microtubule–based motor, and myosin, an actin–based motor, share a similar core structure, indicating that they arose from a common ancestor. However, kinesin lacks the long lever–arm domain that is believed to drive the myosin power stroke. Here, we present evidence that a much smaller region of ca . 10–40 amino acids serves as a mechanical element for kinesin motor proteins. These ‘neck regions’ are class conserved and have distinct structures in plus–end and minus–end–directed kinesin motors. Mutagenesis studies also indicate that the neck regions are involved in coupling ATP hydrolysis and energy into directional motion along the microtubule. We suggest that the kinesin necks drive motion by undergoing a conformational change in which they detach and re–dock onto the catalytic core during the ATPase cycle. Thus, kinesin and myosin have evolved unique mechanical elements that amplify small, nucleotide–dependent conformational changes that occur in their similar catalytic cores.
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Zakrzewski, Przemysław, Maria Jolanta Rędowicz, Folma Buss, and Marta Lenartowska. "Loss of myosin VI expression affects acrosome/acroplaxome complex morphology during mouse spermiogenesis†." Biology of Reproduction 103, no. 3 (2020): 521–33. http://dx.doi.org/10.1093/biolre/ioaa071.
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Abstract During spermiogenesis in mammals, actin filaments and a variety of actin-binding proteins are involved in the formation and function of highly specialized testis-specific structures. Actin-based motor proteins, such as myosin Va and VIIa, play a key role in this complex process of spermatid transformation into mature sperm. We have previously demonstrated that myosin VI (MYO6) is also expressed in mouse testes. It is present in actin-rich structures important for spermatid development, including one of the earliest events in spermiogenesis—acrosome formation. Here, we demonstrate using immunofluorescence, cytochemical, and ultrastructural approaches that MYO6 is involved in maintaining the structural integrity of these specialized actin-rich structures during acrosome biogenesis in mouse. We show that MYO6 together with its binding partner TOM1/L2 is present at/around the spermatid Golgi complex and the nascent acrosome. Depletion of MYO6 in Snell’s waltzer mice causes structural disruptions of the Golgi complex and affects the acrosomal granule positioning within the developing acrosome. In summary, our results suggest that MYO6 plays an anchoring role during the acrosome biogenesis mainly by tethering of different cargo/membranes to highly specialized actin-related structures.
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Furuta, Akane, Misako Amino, Maki Yoshio, Kazuhiro Oiwa, Hiroaki Kojima, and Ken'ya Furuta. "Creating biomolecular motors based on dynein and actin-binding proteins." Nature Nanotechnology 12, no. 3 (2016): 233–37. http://dx.doi.org/10.1038/nnano.2016.238.
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Teves, Maria, Eduardo Roldan, Diego Krapf, Jerome Strauss III, Virali Bhagat, and Paulene Sapao. "Sperm Differentiation: The Role of Trafficking of Proteins." International Journal of Molecular Sciences 21, no. 10 (2020): 3702. http://dx.doi.org/10.3390/ijms21103702.
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Sperm differentiation encompasses a complex sequence of morphological changes that takes place in the seminiferous epithelium. In this process, haploid round spermatids undergo substantial structural and functional alterations, resulting in highly polarized sperm. Hallmark changes during the differentiation process include the formation of new organelles, chromatin condensation and nuclear shaping, elimination of residual cytoplasm, and assembly of the sperm flagella. To achieve these transformations, spermatids have unique mechanisms for protein trafficking that operate in a coordinated fashion. Microtubules and filaments of actin are the main tracks used to facilitate the transport mechanisms, assisted by motor and non-motor proteins, for delivery of vesicular and non-vesicular cargos to specific sites. This review integrates recent findings regarding the role of protein trafficking in sperm differentiation. Although a complete characterization of the interactome of proteins involved in these temporal and spatial processes is not yet known, we propose a model based on the current literature as a framework for future investigations.
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Ghulam, Ali, Rahu Sikander, Dhani Bux Talpur, et al. "IDENTIFYING MOLECULAR FUNCTIONS OF DYNEIN MOTOR PROTEINS USING EXTREME GRADIENT BOOSTING ALGORITHM WITH MACHINE LEARNING." Journal of Mountain Area Research 8 (November 29, 2022): 1. http://dx.doi.org/10.53874/jmar.v8i0.166.
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The majority of cytoplasmic proteins and vesicles move actively primarily to dynein motor proteins, which are the cause of muscle contraction. Moreover, identifying how dynein are used in cells will rely on structural knowledge. Cytoskeletal motor proteins have different molecular roles and structures, and they belong to three superfamilies of dynamin, actin and myosin. Loss of function of specific molecular motor proteins can be attributed to a number of human diseases, such as Charcot-Charcot-Dystrophy and kidney disease. It is crucial to create a precise model to identify dynein motor proteins in order to aid scientists in understanding their molecular role and designing therapeutic targets based on their influence on human disease. Therefore, we develop an accurate and efficient computational methodology is highly desired, especially when using cutting-edge machine learning methods. In this article, we proposed a machine learning-based superfamily of cytoskeletal motor protein locations prediction method called extreme gradient boosting (XGBoost). We get the initial feature set All by extraction the protein features from the sequence and evolutionary data of the amino acid residues named BLOUSM62. Through our successful eXtreme gradient boosting (XGBoost), accuracy score 0.8676%, Precision score 0.8768%, Sensitivity score 0.760%, Specificity score 0.9752% and MCC score 0.7536%. Our method has demonstrated substantial improvements in the performance of many of the evaluation parameters compared to other state-of-the-art methods. This study offers an effective model for the classification of dynein proteins and lays a foundation for further research to improve the efficiency of protein functional classification.
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Coffman, Valerie C., Aaron H. Nile, I.-Ju Lee, Huayang Liu, and Jian-Qiu Wu. "Roles of Formin Nodes and Myosin Motor Activity in Mid1p-dependent Contractile-Ring Assembly during Fission Yeast Cytokinesis." Molecular Biology of the Cell 20, no. 24 (2009): 5195–210. http://dx.doi.org/10.1091/mbc.e09-05-0428.
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Two prevailing models have emerged to explain the mechanism of contractile-ring assembly during cytokinesis in the fission yeast Schizosaccharomyces pombe: the spot/leading cable model and the search, capture, pull, and release (SCPR) model. We tested some of the basic assumptions of the two models. Monte Carlo simulations of the SCPR model require that the formin Cdc12p is present in >30 nodes from which actin filaments are nucleated and captured by myosin-II in neighboring nodes. The force produced by myosin motors pulls the nodes together to form a compact contractile ring. Live microscopy of cells expressing Cdc12p fluorescent fusion proteins shows for the first time that Cdc12p localizes to a broad band of 30–50 dynamic nodes, where actin filaments are nucleated in random directions. The proposed progenitor spot, essential for the spot/leading cable model, usually disappears without nucleating actin filaments. α-Actinin ain1 deletion cells form a normal contractile ring through nodes in the absence of the spot. Myosin motor activity is required to condense the nodes into a contractile ring, based on slower or absent node condensation in myo2-E1 and UCS rng3-65 mutants. Taken together, these data provide strong support for the SCPR model of contractile-ring formation in cytokinesis.
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Evangelista, Marie, Bert M. Klebl, Amy H. Y. Tong, et al. "A Role for Myosin-I in Actin Assembly through Interactions with Vrp1p, Bee1p, and the Arp2/3 Complex." Journal of Cell Biology 148, no. 2 (2000): 353–62. http://dx.doi.org/10.1083/jcb.148.2.353.
Full textAbstract:
Type I myosins are highly conserved actin-based molecular motors that localize to the actin-rich cortex and participate in motility functions such as endocytosis, polarized morphogenesis, and cell migration. The COOH-terminal tail of yeast myosin-I proteins, Myo3p and Myo5p, contains an Src homology domain 3 (SH3) followed by an acidic domain. The myosin-I SH3 domain interacted with both Bee1p and Vrp1p, yeast homologues of human WASP and WIP, adapter proteins that link actin assembly and signaling molecules. The myosin-I acidic domain interacted with Arp2/3 complex subunits, Arc40p and Arc19p, and showed both sequence similarity and genetic redundancy with the COOH-terminal acidic domain of Bee1p (Las17p), which controls Arp2/3-mediated actin nucleation. These findings suggest that myosin-I proteins may participate in a diverse set of motility functions through a role in actin assembly.
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ROMET-LEMONNE, GUILLAUME, EMMANUELE HELFER, VINCENT DELATOUR, et al. "BIOMIMETIC SYSTEMS SHED LIGHT ON ACTIN-BASED MOTILITY DOWN TO THE MOLECULAR SCALE." Biophysical Reviews and Letters 04, no. 01n02 (2009): 5–15. http://dx.doi.org/10.1142/s1793048009000909.
Full textAbstract:
Cell motility, one of the modular activities of living cells, elicits the response of the cell to extra-cellular signals, to move directionally, feed, divide or transport materials. The combined actions of molecular motors and re-modeling of the cytoskeleton generate forces and movement. Here we describe mechanistic approaches of force and movement produced by site-directed assembly of actin filaments. The insight derived from a biochemical analysis of the protein machineries involved in "actin-based motile processes" like cell protrusions, invaginations, organelle propulsion, is used to build reconstituted assays that mimic cellular processes, using several protein machineries known to initiate filament assembly by different mechanisms. Reconstitution of complex self-organized systems presents a broad variety of interests. Reconstituting actin-based movement of a functionalized particle from a minimum number of pure proteins, first used to prove the general thermodynamic principles at work in motility, then was the basis for fully controlled physical measurements of forces produced by polymerization of actin against an obstacle and of the mechanical properties of the resulting polymer arrays. In addition, measurements at the mesoscopic scale (trajectories, velocity, polymer mechanics, fluorescence of specifically labeled components of the actin array, use of mutated proteins) can provide further insight into the molecular mechanisms underlying motility.
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He, Jiayi, Yixing Qiu, Lei Tan, et al. "Understanding the key functions of Myosins in viral infection." Biochemical Society Transactions 50, no. 1 (2022): 597–607. http://dx.doi.org/10.1042/bst20211239.
Full textAbstract:
Myosins, a class of actin-based motor proteins existing in almost any organism, are originally considered only involved in driving muscle contraction, reshaping actin cytoskeleton, and anchoring or transporting cargoes, including protein complexes, organelles, vesicles. However, accumulating evidence reveals that myosins also play vital roles in viral infection, depending on viral species and infection stages. This review systemically summarizes the described various myosins, the performed functions, and the involved mechanisms or molecular pathways during viral infection. Meanwhile, the existing issues are also discussed. Additionally, the important technologies or agents, including siRNA, gene editing, and myosin inhibitors, would facilitate dissecting the actions and mechanisms for described and undescribed myosins, which could be adopted to prevent or control viral infection are also characterized.
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Coluccio, L. M. "Myosin I." American Journal of Physiology-Cell Physiology 273, no. 2 (1997): C347—C359. http://dx.doi.org/10.1152/ajpcell.1997.273.2.c347.
Full textAbstract:
The class I myosins are single-headed, actin-binding, mechanochemical “motor” proteins with heavy chains in the molecular mass range of 110-130 kDa; they do not form filaments. Each myosin I heavy chain is associated with one to six light chains that bind to specific motifs known as IQ domains. In vertebrate myosin I isoforms, the light chain is calmodulin, which is thought to regulate motor activity. Proteins similar to calmodulin are associated with myosin I isoforms from lower eukaryotes. Some myosin I isoforms from lower eukaryotes are regulated by phosphorylation; however, the phosphorylation site is not present in vertebrate myosin I isoforms. Based on sequence analyses of the amino terminal “head” domains, myosin I can be subdivided into several subclasses. Analyses of the biochemical properties of the isolated molecules and localization studies support the proposal of roles for these molecules in intracellular trafficking and changes in membrane structure. Our present understanding of the properties of these molecules and their proposed roles is reviewed here.
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Lee, Min Joung, Yunseon Jang, Jeongsu Han, et al. "Endothelial-specific Crif1 deletion induces BBB maturation and disruption via the alteration of actin dynamics by impaired mitochondrial respiration." Journal of Cerebral Blood Flow & Metabolism 40, no. 7 (2020): 1546–61. http://dx.doi.org/10.1177/0271678x19900030.
Full textAbstract:
Cerebral endothelial cells (ECs) require junctional proteins to maintain blood–brain barrier (BBB) integrity, restricting toxic substances and controlling peripheral immune cells with a higher concentration of mitochondria than ECs of peripheral capillaries. The mechanism underlying BBB disruption by defective mitochondrial oxidative phosphorylation (OxPhos) is unclear in a mitochondria-related gene-targeted animal model. To assess the role of EC mitochondrial OxPhos function in the maintenance of the BBB, we developed an EC-specific CR6-interactin factor1 ( Crif1) deletion mouse. We clearly observed defects in motor behavior, uncompacted myelin and leukocyte infiltration caused by BBB maturation and disruption in this mice. Furthermore, we investigated the alteration in the actin cytoskeleton, which interacts with junctional proteins to support BBB integrity. Loss of Crif1 led to reorganization of the actin cytoskeleton and a decrease in tight junction-associated protein expression through an ATP production defect in vitro and in vivo. Based on these results, we suggest that mitochondrial OxPhos is important for the maturation and maintenance of BBB integrity by supplying ATP to cerebral ECs.
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Cornfine, Susanne, Mirko Himmel, Petra Kopp, et al. "The kinesin KIF9 and reggie/flotillin proteins regulate matrix degradation by macrophage podosomes." Molecular Biology of the Cell 22, no. 2 (2011): 202–15. http://dx.doi.org/10.1091/mbc.e10-05-0394.
Full textAbstract:
Podosomes are actin-based matrix contacts in a variety of cell types, most notably monocytic cells, and are characterized by their ability to lyse extracellular matrix material. Besides their dependence on actin regulation, podosomes are also influenced by microtubules and microtubule-dependent transport processes. Here we describe a novel role for KIF9, a previously little-characterized member of the kinesin motor family, in the regulation of podosomes in primary human macrophages. We find that small interfering RNA (siRNA)/short-hairpin RNA–induced knockdown of KIF9 significantly affects both numbers and matrix degradation of podosomes. Overexpression and microinjection experiments reveal that the unique C-terminal region of KIF9 is crucial for these effects, presumably through binding of specific interactors. Indeed, we further identify reggie-1/flotillin-2, a signaling mediator between intracellular vesicles and the cell periphery, as an interactor of the KIF9 C-terminus. Reggie-1 dynamically colocalizes with KIF9 in living cells, and, consistent with KIF9-mediated effects, siRNA-induced knockdown of reggies/flotillins significantly impairs matrix degradation by podosomes. In sum, we identify the kinesin KIF9 and reggie/flotillin proteins as novel regulators of macrophage podosomes and show that their interaction is critical for the matrix-degrading ability of these structures.
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Stødkilde, Lene, Johan Palmfeldt, Line Nilsson, et al. "Proteomic identification of early changes in the renal cytoskeleton in obstructive uropathy." American Journal of Physiology-Renal Physiology 306, no. 12 (2014): F1429—F1441. http://dx.doi.org/10.1152/ajprenal.00244.2013.
Full textAbstract:
Bilateral ureteral obstruction (BUO) is associated with renal damage and impaired ability to concentrate urine and is known to induce alterations in an array of kidney proteins. The aim of this study was to identify acute proteomic alterations induced by BUO. Rats were subjected to BUO for 2, 6, or 24 h. Mass spectrometry-based proteomics was performed on the renal inner medulla, and protein changes in the obstructed group were identified. Significant changes were successfully identified for 109 proteins belonging to different biological classes. Interestingly, proteins belonging to the cytoskeleton and proteins related to cytoskeletal regulation were found to be biologically enriched in BUO using online-accessible tools. Western blots confirmed the selected results, demonstrating acute downregulation of proteins belonging to all three cytoskeletal components. The microfilament protein β-actin and the intermediate filament proteins pankeratin and vimentin were all downregulated. β-Tubulin, an important microtubular protein, was found to be significantly downregulated after 24 h. Also, there was significant upregulation of cofilin, an actin-binding protein known to be upregulated in other nephropathy models. Furthermore, both upregulation and downregulation of cytoskeletal motor and regulatory proteins were observed. These findings were confirmed by immunohistochemistry, which clearly showed alterations in labeling in the inner medulla. Interestingly, we were able to confirm selected results in mpkCCD cells exposed to mechanical stretch. Our findings add to the knowledge of BUO-induced acute changes in the renal cytoskeleton and suggest that these molecular changes are partly mediated by increased stretch of the cells during obstruction.
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DeGiorgis, Joseph A., Thomas S. Reese, and Elaine L. Bearer. "Association of a Nonmuscle Myosin II with Axoplasmic Organelles." Molecular Biology of the Cell 13, no. 3 (2002): 1046–57. http://dx.doi.org/10.1091/mbc.01-06-0315.
Full textAbstract:
Association of motor proteins with organelles is required for the motors to mediate transport. Because axoplasmic organelles move on actin filaments, they must have associated actin-based motors, most likely members of the myosin superfamily. To gain a better understanding of the roles of myosins in the axon we used the giant axon of the squid, a powerful model for studies of axonal physiology. First, a ∼220 kDa protein was purified from squid optic lobe, using a biochemical protocol designed to isolate myosins. Peptide sequence analysis, followed by cloning and sequencing of the full-length cDNA, identified this ∼220 kDa protein as a nonmuscle myosin II. This myosin is also present in axoplasm, as determined by two independent criteria. First, RT-PCR using sequence-specific primers detected the transcript in the stellate ganglion, which contains the cell bodies that give rise to the giant axon. Second, Western blot analysis using nonmuscle myosin II isotype-specific antibodies detected a single ∼220 kDa band in axoplasm. Axoplasm was fractionated through a four-step sucrose gradient after 0.6 M KI treatment, which separates organelles from cytoskeletal components. Of the total nonmuscle myosin II in axoplasm, 43.2% copurified with organelles in the 15% sucrose fraction, while the remainder (56.8%) was soluble and found in the supernatant. This myosin decorates the cytoplasmic surface of 21% of the axoplasmic organelles, as demonstrated by immunogold electron-microscopy. Thus, nonmuscle myosin II is synthesized in the cell bodies of the giant axon, is present in the axon, and is associated with isolated axoplasmic organelles. Therefore, in addition to myosin V, this myosin is likely to be an axoplasmic organelle motor.
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Munchow, S., C. Sauter, and R. P. Jansen. "Association of the class V myosin Myo4p with a localised messenger RNA in budding yeast depends on She proteins." Journal of Cell Science 112, no. 10 (1999): 1511–18. http://dx.doi.org/10.1242/jcs.112.10.1511.
Full textAbstract:
Asymmetric distribution of messenger RNAs is a widespread mechanism to localize synthesis of specific protein to distinct sites in the cell. Although not proven yet there is considerable evidence that mRNA localisation is an active process that depends on the activity of cytoskeletal motor proteins. To date, the only motor protein with a specific role in mRNA localisation is the budding yeast type V myosin Myo4p. Myo4p is required for the localisation of ASH1 mRNA, encoding a transcriptional repressor that is essential for differential expression of the HO gene and mating type switching in budding yeast. Mutations in Myo4p, in proteins of the actin cytoskeleton, and in four other specific genes, SHE2-SHE5 disrupt the daughter-specific localisation of ASH1 mRNA. In order to understand if Myo4p is directly participating in mRNA transport, we used in situ colocalisation and coprecipitation of Myo4p and ASH1 mRNA to test for their interaction. Our results indicate an association of Myo4p and ASH1 mRNA that depends on the activity of two other genes involved in ASH1 mRNA localisation, SHE2 and SHE3. This strongly suggests a direct role of Myo4p myosin as a transporter of localised mRNAs, convincingly supporting the concept of motor-protein based mRNA localisation.
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Zakrzewski, Przemysław, Anna Suwińska, Robert Lenartowski, Maria Jolanta Rędowicz, Folma Buss, and Marta Lenartowska. "Myosin VI maintains the actin-dependent organization of the tubulobulbar complexes required for endocytosis during mouse spermiogenesis†‡." Biology of Reproduction 102, no. 4 (2020): 863–75. http://dx.doi.org/10.1093/biolre/ioz232.
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Abstract Myosin VI (MYO6) is an actin-based motor that has been implicated in a wide range of cellular processes, including endocytosis and the regulation of actin dynamics. MYO6 is crucial for actin/membrane remodeling during the final step of Drosophila spermatogenesis, and MYO6-deficient males are sterile. This protein also localizes to actin-rich structures involved in mouse spermiogenesis. Although loss of MYO6 in Snell’s waltzer knock-out (KO) mice causes several defects and shows reduced male fertility, no studies have been published to address the role of MYO6 in sperm development in mouse. Here we demonstrate that MYO6 and some of its binding partners are present at highly specialized actin-based structures, the apical tubulobulbar complexes (TBCs), which mediate endocytosis of the intercellular junctions at the Sertoli cell-spermatid interface, an essential process for sperm release. Using electron and light microscopy and biochemical approaches, we show that MYO6, GIPC1 and TOM1/L2 form a complex in testis and localize predominantly to an early endocytic APPL1-positive compartment of the TBCs that is distinct from EEA1-positive early endosomes. These proteins also associate with the TBC actin-free bulbular region. Finally, our studies using testis from Snell’s waltzer males show that loss of MYO6 causes disruption of the actin cytoskeleton and disorganization of the TBCs and leads to defects in the distribution of the MYO6-positive early APPL1-endosomes. Taken together, we report here for the first time that lack of MYO6 in mouse testis reduces male fertility and disrupts spatial organization of the TBC-related endocytic compartment during the late phase of spermiogenesis.
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Tabakaeva, Oksana, та Anton Tabakaev. "Proteins Features of the Far Eastern Region Bivalve Mollusk Mactra Сhinensis". Food Industry 5, № 1 (2020): 65–70. http://dx.doi.org/10.29141/2500-1922-2020-5-1-8.
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Bivalve mollusk are protein raw materials, their soft tissues are characterized by a hard-rubbery consistency due to its proteins characteristics and should be considered when processing into food. The proteins fractional composition study of different groups (water-soluble, myofibrillar, and stroma) is an urgent task, since it is possible to justify the processing technology based on the obtained data. The article presents the fractional composition study results of the water-soluble proteins and peptides, the molecular mass distribution of the separate components of myofibrillary proteins and muscle tissue stroma proteins of the Mactra Chinensis mollusk motor muscle. The researchers noted that the total amount of the high-molecular fraction (molecular weight above 10 kDa) is 62.16 %, and the total peptide fraction amount (molecular weight below 10 kDa) is 37.84 %. There are four main components in myofibrillar proteins – myosin, actin, troponin complex components, and collagen. The content of the main myofibrillar protein that is myosin of various polymerization degrees of is 69.3 %; heavy myosin chains – 30.5 % of the total myofibrillar proteins content and 44.0 % of the relative content of the total myosin content; light myosin chains – 38.8 % of the total myofibrillar proteins content and 56.0 % of the relative content of the total myosin content. The authors determined that actin (molecular weight 43 kDa) and troponin complex components (molecular weight from 15 to 30 kDa) are approximately equal in content. The collagen content (molecular weight more than 300 kDa) in the myofibrillar fraction is only 8.2 %. Stroma proteins are represented by two main fractions with molecular weights of more than 250 and 500 kDa. Collagen is the predominant stroma protein, its content account for 62.6 %. There is a high connectin content in stroma proteins.
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Diefenbach, Thomas J., Vaughan M. Latham, Dean Yimlamai, Canwen A. Liu, Ira M. Herman, and Daniel G. Jay. "Myosin 1c and myosin IIB serve opposing roles in lamellipodial dynamics of the neuronal growth cone." Journal of Cell Biology 158, no. 7 (2002): 1207–17. http://dx.doi.org/10.1083/jcb.200202028.
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The myosin family of motor proteins is implicated in mediating actin-based growth cone motility, but the roles of many myosins remain unclear. We previously implicated myosin 1c (M1c; formerly myosin Iβ) in the retention of lamellipodia (Wang et al., 1996). Here we address the role of myosin II (MII) in chick dorsal root ganglion neuronal growth cone motility and the contribution of M1c and MII to retrograde F-actin flow using chromophore-assisted laser inactivation (CALI). CALI of MII reduced neurite outgrowth and growth cone area by 25%, suggesting a role for MII in lamellipodial expansion. Micro-CALI of MII caused a rapid reduction in local lamellipodial protrusion in growth cones with no effects on filopodial dynamics. This is opposite to micro-CALI of M1c, which caused an increase in lamellipodial protrusion. We used fiduciary beads (Forscher et al., 1992) to observe retrograde F-actin flow during the acute loss of M1c or MII. Micro-CALI of M1c reduced retrograde bead flow by 76%, whereas micro-CALI of MII or the MIIB isoform did not. Thus, M1c and MIIB serve opposite and nonredundant roles in regulating lamellipodial dynamics, and M1c activity is specifically required for retrograde F-actin flow.
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Casoni, Filippo, Manuela Basso, Tania Massignan, et al. "Protein Nitration in a Mouse Model of Familial Amyotrophic Lateral Sclerosis." Journal of Biological Chemistry 280, no. 16 (2005): 16295–304. http://dx.doi.org/10.1074/jbc.m413111200.
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Multiple mechanisms have been proposed to contribute to amyotrophic lateral sclerosis (ALS) pathogenesis, including oxidative stress. Early evidence of a role for oxidative damage was based on the finding, in patients and murine models, of high levels of markers, such as free nitrotyrosine (NT). However, no comprehensive study on the protein targets of nitration in ALS has been reported. We found an increased level of NT immunoreactivity in spinal cord protein extracts of a transgenic mouse model of familial ALS (FALS) at a presymptomatic stage of the disease compared with age-matched controls. NT immunoreactivity is increased in the soluble fraction of spinal cord homogenates and is found as a punctate staining in motor neuron perikarya of presymptomatic FALS mice. Using a proteome-based strategy, we identified proteins nitratedin vivo, under physiological or pathological conditions, and compared their level of specific nitration. α- and γ-enolase, ATP synthase β chain, and heat shock cognate 71-kDa protein and actin were overnitrated in presymptomatic FALS mice. We identified by matrix-assisted laser desorption/ionization mass spectrometry 16 sites of nitration in proteins oxidizedin vivo. In particular, α-enolase nitration at Tyr43, target also of phosphorylation, brings additional evidence on the possible interference of nitration with phosphorylation. In conclusion, we propose that protein nitration may have a role in ALS pathogenesis, acting directly by inhibiting the function of specific proteins and indirectly interfering with protein degradation pathways and phosphorylation cascades.
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Lu, Ling, Yuh-Ru Julie Lee, Ruiqin Pan, Julin N. Maloof, and Bo Liu. "An Internal Motor Kinesin Is Associated with the Golgi Apparatus and Plays a Role in Trichome Morphogenesis in Arabidopsis." Molecular Biology of the Cell 16, no. 2 (2005): 811–23. http://dx.doi.org/10.1091/mbc.e04-05-0400.
Full textAbstract:
Members of the kinesin superfamily are microtubule-based motor proteins that transport molecules/organelles along microtubules. We have identified similar internal motor kinesins, Kinesin-13A, from the cotton Gossypium hirsutum and Arabidopsis thaliana. Their motor domains share high degree of similarity with those of internal motor kinesins of animals and protists in the MCAK/Kinesin13 subfamily. However, no significant sequence similarities were detected in sequences outside the motor domain. In Arabidopsis plants carrying the T-DNA knockout kinesin-13a-1 and kinesin-13a-2 mutations at the Kinesin-13A locus, >70% leaf trichomes had four branches, whereas wild-type trichomes had three. Immunofluorescent results showed that AtKinesin-13A and GhKinesin-13A localized to entire Golgi stacks. In both wild-type and kinesin-13a mutant cells, the Golgi stacks were frequently associated with microtubules and with actin microfilaments. Aggregation/clustering of Golgi stacks was often observed in the kinesin-13a mutant trichomes and other epidermal cells. This suggested that the distribution of the Golgi apparatus in cell cortex might require microtubules and Kinesin-13A, and the organization of Golgi stacks could play a regulatory role in trichome morphogenesis. Our results also indicate that plant kinesins in the MCAK/Kinesin-13 subfamily have evolved to take on different tasks than their animal counterparts.
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Marchelletta, Ronald R., Damon T. Jacobs, Joel E. Schechter, Richard E. Cheney, and Sarah F. Hamm-Alvarez. "The class V myosin motor, myosin 5c, localizes to mature secretory vesicles and facilitates exocytosis in lacrimal acini." American Journal of Physiology-Cell Physiology 295, no. 1 (2008): C13—C28. http://dx.doi.org/10.1152/ajpcell.00330.2007.
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We investigated the role of the actin-based myosin motor, myosin 5c (Myo5c) in vesicle transport in exocrine secretion. Lacrimal gland acinar cells (LGAC) are the major source for the regulated secretion of proteins from the lacrimal gland into the tear film. Confocal fluorescence and immunogold electron microscopy revealed that Myo5c was associated with secretory vesicles in primary rabbit LGAC. Upon stimulation of secretion with the muscarinic agonist, carbachol, Myo5c was also detected in association with actin-coated fusion intermediates. Adenovirus-mediated expression of green fluorescent protein (GFP) fused to the tail domain of Myo5c (Ad-GFP-Myo5c-tail) showed that this protein was localized to secretory vesicles. Furthermore, its expression induced a significant ( P ≤ 0.05) decrease in carbachol-stimulated release of two secretory vesicle content markers, secretory component and syncollin-GFP. Adenovirus-mediated expression of GFP appended to the full-length Myo5c (Ad-GFP-Myo5c-full) was used in parallel with adenovirus-mediated expression of GFP-Myo5c-tail in LGAC to compare various parameters of secretory vesicles labeled with either GFP-labeled protein in resting and stimulated LGAC. These studies revealed that the carbachol-stimulated increase in secretory vesicle diameter associated with compound fusion of secretory vesicles that was also exhibited by vesicles labeled with GFP-Myo5c-full was impaired in vesicles labeled with GFP-Myo5c-tail. A significant decrease in GFP labeling of actin-coated fusion intermediates was also seen in carbachol-stimulated LGAC transduced with GFP-Myo5c-tail relative to LGAC transduced with GFP-Myo5c-full. These results suggest that Myo5c participates in apical exocytosis of secretory vesicles.
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Pollard, Thomas D., and E. Michael Ostap. "The Chemical Mechanism of Myosin-I: Implications for Actin-based Motility and the Evolution of the Myosin Family of Motor Proteins." Cell Structure and Function 21, no. 5 (1996): 351–56. http://dx.doi.org/10.1247/csf.21.351.
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Barvitenko, Nadezhda, Muhammad Aslam, Alfons Lawen, et al. "Two Motors and One Spring: Hypothetic Roles of Non-Muscle Myosin II and Submembrane Actin-Based Cytoskeleton in Cell Volume Sensing." International Journal of Molecular Sciences 22, no. 15 (2021): 7967. http://dx.doi.org/10.3390/ijms22157967.
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Changes in plasma membrane curvature and intracellular ionic strength are two key features of cell volume perturbations. In this hypothesis we present a model of the responsible molecular apparatus which is assembled of two molecular motors [non-muscle myosin II (NMMII) and protrusive actin polymerization], a spring [a complex between the plasma membrane (PM) and the submembrane actin-based cytoskeleton (smACSK) which behaves like a viscoelastic solid] and the associated signaling proteins. We hypothesize that this apparatus senses changes in both the plasma membrane curvature and the ionic strength and in turn activates signaling pathways responsible for regulatory volume increase (RVI) and regulatory volume decrease (RVD). During cell volume changes hydrostatic pressure (HP) changes drive alterations in the cell membrane curvature. HP difference has opposite directions in swelling versus shrinkage, thus allowing distinction between them. By analogy with actomyosin contractility that appears to sense stiffness of the extracellular matrix we propose that NMMII and actin polymerization can actively probe the transmembrane gradient in HP. Furthermore, NMMII and protein-protein interactions in the actin cortex are sensitive to ionic strength. Emerging data on direct binding to and regulating activities of transmembrane mechanosensors by NMMII and actin cortex provide routes for signal transduction from transmembrane mechanosensors to cell volume regulatory mechanisms.
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Karpov, Pavel, Aleksey Raevsky, Maxim Korablyov, and Yaroslav Blume. "Identification of Plant Homologues of Dual Specificity Yak1-Related Kinases." Computational Biology Journal 2014 (December 8, 2014): 1–14. http://dx.doi.org/10.1155/2014/909268.
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Currently, Dual Specificity YAK1-Related Kinases (MNB/DYRK) were found in slime molds, protista, fungi, and animals, but the existence of plant homologues is still unclear. In the present study, we have identified 14 potential plant homologues with the previously unknown functions, based on the strong sequence similarity. The results of bioinformatics analysis revealed their correspondence to DYRK1A, DYRK1B, DYRK3, and DYRK4. For two plant homologues of animal DYRK1A from Physcomitrella patens and Arabidopsis thaliana spatial structures of catalytic domains were predicted, as well as their complexes with ADP and selective inhibitor d15. Comparative analysis of 3D-structures of the human DYRK1A and plant homologues, their complexes with the specific inhibitors, and results of molecular dynamics confirm their structural and functional similarity with high probability. Preliminary data indicate the presence of potential MNB/DYRK specific phosphorylation sites in such proteins associated with plant cytoskeleton as plant microtubule-associated proteins WVD2 and WDL1, and FH5 and SCAR2 involved in the organization and polarity of the actin cytoskeleton and some kinesin-like microtubule motor proteins.
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Stoffler, H. E., U. Honnert, C. A. Bauer, et al. "Targeting of the myosin-I myr 3 to intercellular adherens type junctions induced by dominant active Cdc42 in HeLa cells." Journal of Cell Science 111, no. 18 (1998): 2779–88. http://dx.doi.org/10.1242/jcs.111.18.2779.
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Myr 3, a member of the myosin-I family from rat, is shown in this study to be localized at adherens-type intercellular junctions in epithelial and nonepithelial tissues. Formation of intercellular junctions and the accompanying recruitment of myr 3 to these junctions involves signaling by the Rho subfamily of small GTP-binding proteins. This conclusion is based on studies with HtTA-1 HeLa cells that were induced by overexpression of constitutively active Cdc42Hs to form typical adherens-type intercellular junctions enriched in cadherins (N-cadherin), beta-catenin, filamentous actin and myr 3. Recruitement of myr 3 to Cdc42-induced adherens junctions in HeLa cells was dependent on a short region of the tail domain and a functional myosin motor domain, but was independent of its myosin-I tail homology and SH3 regions. Overexpression of constitutively active Rac1 induced a distinct type of adherens junction in HeLa cells that was characterized by elaborate intercellular interdigitations enriched in N-cadherin, beta-catenin and F-actin. Myr 3 was often present, but not specifically enriched in the intercellular junctions induced by constitutively active Rac1.
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Raposo, Graça, Marie-Neige Cordonnier, Danièle Tenza, et al. "Association of Myosin I Alpha with Endosomes and Lysosomes in Mammalian Cells." Molecular Biology of the Cell 10, no. 5 (1999): 1477–94. http://dx.doi.org/10.1091/mbc.10.5.1477.
Full textAbstract:
Myosin Is, which constitute a ubiquitous monomeric subclass of myosins with actin-based motor properties, are associated with plasma membrane and intracellular vesicles. Myosin Is have been proposed as key players for membrane trafficking in endocytosis or exocytosis. In the present paper we provide biochemical and immunoelectron microscopic evidence indicating that a pool of myosin I alpha (MMIα) is associated with endosomes and lysosomes. We show that the overproduction of MMIα or the production of nonfunctional truncated MMIα affects the distribution of the endocytic compartments. We also show that truncated brush border myosin I proteins, myosin Is that share 78% homology with MMIα, promote the dissociation of MMIα from vesicular membranes derived from endocytic compartments. The analysis at the ultrastructural level of cells producing these brush border myosin I truncated proteins shows that the delivery of the fluid phase markers from endosomes to lysosomes is impaired. MMIα might therefore be involved in membrane trafficking occurring between endosomes and lysosomes.
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Månsson, Alf. "Hypothesis: Single Actomyosin Properties Account for Ensemble Behavior in Active Muscle Shortening and Isometric Contraction." International Journal of Molecular Sciences 21, no. 21 (2020): 8399. http://dx.doi.org/10.3390/ijms21218399.
Full textAbstract:
Muscle contraction results from cyclic interactions between myosin II motors and actin with two sets of proteins organized in overlapping thick and thin filaments, respectively, in a nearly crystalline lattice in a muscle sarcomere. However, a sarcomere contains a huge number of other proteins, some with important roles in muscle contraction. In particular, these include thin filament proteins, troponin and tropomyosin; thick filament proteins, myosin binding protein C; and the elastic protein, titin, that connects the thin and thick filaments. Furthermore, the order and 3D organization of the myofilament lattice may be important per se for contractile function. It is possible to model muscle contraction based on actin and myosin alone with properties derived in studies using single molecules and biochemical solution kinetics. It is also possible to reproduce several features of muscle contraction in experiments using only isolated actin and myosin, arguing against the importance of order and accessory proteins. Therefore, in this paper, it is hypothesized that “single molecule actomyosin properties account for the contractile properties of a half sarcomere during shortening and isometric contraction at almost saturating Ca concentrations”. In this paper, existing evidence for and against this hypothesis is reviewed and new modeling results to support the arguments are presented. Finally, further experimental tests are proposed, which if they corroborate, at least approximately, the hypothesis, should significantly benefit future effective analysis of a range of experimental studies, as well as drug discovery efforts.
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Geva, Polina, Konstantin Komoshvili, and Stella Liberman-Aronov. "Two- and Three-Dimensional Tracking of MFA2 mRNA Molecules in Mating Yeast." Cells 9, no. 10 (2020): 2151. http://dx.doi.org/10.3390/cells9102151.
Full textAbstract:
Intracellular mRNA transport contributes to the spatio-temporal regulation of mRNA function and localized translation. In the budding yeast, Saccharomyces cerevisiae, asymmetric mRNA transport localizes ~30 specific mRNAs including those encoding polarity and secretion factors, to the bud tip. The underlying process involves RNA-binding proteins (RBPs), molecular motors, processing bodies (PBs), and the actin cytoskeleton. Recently, pheromone a-factor expression in mating yeast was discovered to depend on proper localization of its mRNA, MFA2 mRNAs in conjunction with PBs cluster at the shmoo tip to form “mating bodies”, from which a-factor is locally expressed. The mechanism ensuring the correct targeting of mRNA to the shmoo tip is poorly understood. Here we analyzed the kinetics and trajectories of MFA2 mRNA transport in living, alpha-factor treated yeast. Two- (2D) and three-dimensional (3D) analyses allowed us to reconstruct the granule tracks and estimate granule velocities. Tracking analysis of single MFA2 mRNA granules, labeled using a fluorescent aptamer system, demonstrated three types movement: vibrational, oscillatory and translocational. The mRNA granule transport was complex; a granule could change its movement behavior and composition during its journey to the shmoo. Processing body assembly and the actin-based motor, Myo4p, were involved in movement of MFA2 mRNA to the shmoo, but neither was required, indicating that multiple mechanisms for translocation were at play. Our visualization studies present a dynamic view of the localization mechanism in shmoo-bearing cells.
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Blanc, Florian, Tatiana Isabet, Hannah Benisty, H. Lee Sweeney, Marco Cecchini, and Anne Houdusse. "An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics." Proceedings of the National Academy of Sciences 115, no. 24 (2018): 6213–18. http://dx.doi.org/10.1073/pnas.1711512115.
Full textAbstract:
Myosins form a class of actin-based, ATPase motor proteins that mediate important cellular functions such as cargo transport and cell motility. Their functional cycle involves two large-scale swings of the lever arm: the force-generating powerstroke, which takes place on actin, and the recovery stroke during which the lever arm is reprimed into an armed configuration. Previous analyses of the prerecovery (postrigor) and postrecovery (prepowerstroke) states predicted that closure of switch II in the ATP binding site precedes the movement of the converter and the lever arm. Here, we report on a crystal structure of myosin VI, called pretransition state (PTS), which was solved at 2.2 Å resolution. Structural analysis and all-atom molecular dynamics simulations are consistent with PTS being an intermediate along the recovery stroke, where the Relay/SH1 elements adopt a postrecovery conformation, and switch II remains open. In this state, the converter appears to be largely uncoupled from the motor domain and explores an ensemble of partially reprimed configurations through extensive, reversible fluctuations. Moreover, we found that the free energy cost of hydrogen-bonding switch II to ATP is lowered by more than 10 kcal/mol compared with the prerecovery state. These results support the conclusion that closing of switch II does not initiate the recovery stroke transition in myosin VI. Rather, they suggest a mechanism in which lever arm repriming would be mostly driven by thermal fluctuations and eventually stabilized by the switch II interaction with the nucleotide in a ratchet-like fashion.
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Jacobs, Damon T., Roberto Weigert, Kyle D. Grode, Julie G. Donaldson, and Richard E. Cheney. "Myosin Vc Is a Molecular Motor That Functions in Secretory Granule Trafficking." Molecular Biology of the Cell 20, no. 21 (2009): 4471–88. http://dx.doi.org/10.1091/mbc.e08-08-0865.
Full textAbstract:
Class V myosins are actin-based motor proteins that have critical functions in organelle trafficking. Of the three class V myosins expressed in mammals, relatively little is known about Myo5c except that it is abundant in exocrine tissues. Here we use MCF-7 cells to identify the organelles that Myo5c associates with, image the dynamics of Myo5c in living cells, and test the functions of Myo5c. Endogenous Myo5c localizes to two distinct compartments: small puncta and slender tubules. Myo5c often exhibits a highly polarized distribution toward the leading edge in migrating cells and is clearly distinct from the Myo5a or Myo5b compartments. Imaging with GFP-Myo5c reveals that Myo5c puncta move slowly (∼30 nm/s) and microtubule independently, whereas tubules move rapidly (∼440 nm/s) and microtubule dependently. Myo5c puncta colocalize with secretory granule markers such as chromogranin A and Rab27b, whereas Myo5c tubules are labeled by Rab8a. TIRF imaging indicates that the granules can be triggered to undergo secretion. To test if Myo5c functions in granule trafficking, we used the Myo5c tail as a dominant negative and found that it dramatically perturbs the distribution of granule markers. These results provide the first live-cell imaging of Myo5c and indicate that Myo5c functions in secretory granule trafficking.