Artículos de revistas: "Midbodt Remnant"

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McDougall, Alex, Celine Hebras, Gerard Pruliere, David Burgess, Vlad Costache, Remi Dumollard y Janet Chenevert. "Role of PB1 Midbody Remnant Creating Tethered Polar Bodies during Meiosis II". Genes 11, n.º 12 (24 de noviembre de 2020): 1394. http://dx.doi.org/10.3390/genes11121394.

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Polar body (PB) formation is an extreme form of unequal cell division that occurs in oocytes due to the eccentric position of the small meiotic spindle near the oocyte cortex. Prior to PB formation, a chromatin-centered process causes the cortex overlying the meiotic chromosomes to become polarized. This polarized cortical subdomain marks the site where a cortical protrusion or outpocket forms at the oocyte surface creating the future PBs. Using ascidians, we observed that PB1 becomes tethered to the fertilized egg via PB2, indicating that the site of PB1 cytokinesis directed the precise site for PB2 emission. We therefore studied whether the midbody remnant left behind following PB1 emission was involved, together with the egg chromatin, in defining the precise cortical site for PB2 emission. During outpocketing of PB2 in ascidians, we discovered that a small structure around 1 µm in diameter protruded from the cortical outpocket that will form the future PB2, which we define as the “polar corps”. As emission of PB2 progressed, this small polar corps became localized between PB2 and PB1 and appeared to link PB2 to PB1. We tested the hypothesis that this small polar corps on the surface of the forming PB2 outpocket was the midbody remnant from the previous round of PB1 cytokinesis. We had previously discovered that Plk1::Ven labeled midbody remnants in ascidian embryos. We therefore used Plk1::Ven to follow the dynamics of the PB1 midbody remnant during meiosis II. Plk1::Ven strongly labeled the small polar corps that formed on the surface of the cortical outpocket that created PB2. Following emission of PB2, this polar corps was rich in Plk1::Ven and linked PB2 to PB1. By labelling actin (with TRITC-Phalloidin) we also demonstrated that actin accumulates at the midbody remnant and also forms a cortical cap around the midbody remnant in meiosis II that prefigured the precise site of cortical outpocketing during PB2 emission. Phalloidin staining of actin and immunolabelling of anti-phospho aPKC during meiosis II in fertilized eggs that had PB1 removed suggested that the midbody remnant remained within the fertilized egg following emission of PB1. Dynamic imaging of microtubules labelled with Ens::3GFP, MAP7::GFP or EB3::3GFP showed that one pole of the second meiotic spindle was located near the midbody remnant while the other pole rotated away from the cortex during outpocketing. Finally, we report that failure of the second meiotic spindle to rotate can lead to the formation of two cortical outpockets at anaphase II, one above each set of chromatids. It is not known whether the midbody remnant of PB1 is involved in directing the precise location of PB2 since our data are correlative in ascidians. However, a review of the literature indicates that PB1 is tethered to the egg surface via PB2 in several species including members of the cnidarians, lophotrochozoa and echinoids, suggesting that the midbody remnant formed during PB1 emission may be involved in directing the precise site of PB2 emission throughout the invertebrates.

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2

Bernabé-Rubio, Miguel, Germán Andrés, Javier Casares-Arias, Jaime Fernández-Barrera, Laura Rangel, Natalia Reglero-Real, David C. Gershlick et al. "Novel role for the midbody in primary ciliogenesis by polarized epithelial cells". Journal of Cell Biology 214, n.º 3 (25 de julio de 2016): 259–73. http://dx.doi.org/10.1083/jcb.201601020.

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The primary cilium is a membrane protrusion that is crucial for vertebrate tissue homeostasis and development. Here, we investigated the uncharacterized process of primary ciliogenesis in polarized epithelial cells. We show that after cytokinesis, the midbody is inherited by one of the daughter cells as a remnant that initially locates peripherally at the apical surface of one of the daughter cells. The remnant then moves along the apical surface and, once proximal to the centrosome at the center of the apical surface, enables cilium formation. The physical removal of the remnant greatly impairs ciliogenesis. We developed a probabilistic cell population–based model that reproduces the experimental data. In addition, our model explains, solely in terms of cell area constraints, the various observed transitions of the midbody, the beginning of ciliogenesis, and the accumulation of ciliated cells. Our findings reveal a biological mechanism that links the three microtubule-based organelles—the midbody, the centrosome, and the cilium—in the same cellular process.

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3

Singh, Deepika y Christian Pohl. "A function for the midbody remnant in embryonic patterning". Communicative & Integrative Biology 7, n.º 3 (3 de abril de 2014): e28533. http://dx.doi.org/10.4161/cib.28533.

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4

Ott, Carolyn M. "Midbody remnant licenses primary cilia formation in epithelial cells". Journal of Cell Biology 214, n.º 3 (1 de agosto de 2016): 237–39. http://dx.doi.org/10.1083/jcb.201607046.

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Tethered midbody remnants dancing across apical microvilli, encountering the centrosome, and beckoning forth a cilium—who would have guessed this is how polarized epithelial cells coordinate the end of mitosis and the beginning of ciliogenesis? New evidence from Bernabé-Rubio et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601020) supports this emerging model.

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5

McNeely, Katrina C. y Noelle D. Dwyer. "Cytokinesis and postabscission midbody remnants are regulated during mammalian brain development". Proceedings of the National Academy of Sciences 117, n.º 17 (9 de abril de 2020): 9584–93. http://dx.doi.org/10.1073/pnas.1919658117.

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Building a brain of the proper size and structure requires neural stem cells (NSCs) to divide with tight temporal and spatial control to produce different daughter cell types in proper numbers and sequence. Mammalian NSCs in the embryonic cortex must maintain their polarized epithelial structure as they undergo both early proliferative divisions and later neurogenic divisions. To do this, they undergo a polarized form of cytokinesis at the apical membrane that is not well understood. Here, we investigate whether polarized furrowing and abscission in mouse NSCs are regulated differently at earlier and later stages and in a cytokinesis mutant, Kif20b. This mutant was previously shown to have microcephaly and elevated apoptosis of NSCs. We developed methods to live image furrow ingression and midbody abscission in NSCs within cortical explants. We find that polarized furrow ingression occurs at a steady rate and completes in ∼15 min at two different ages. However, ingression is slower in a subset of Kif20b mutant NSCs. Abscission is usually observed on both sides of the midbody and takes 65 to 75 min to complete. Surprisingly, abscission is accelerated in the Kif20b mutant NSCs. Postabscission midbody remnants are observed at the apical membranes of daughter cells and are much more abundant in early-stage cortices. After NSC divisions in vitro, midbody remnants are more often retained on the daughter cells of early proliferative divisions. Altogether, these results suggest that regulation of abscission timing and midbody remnants in embryonic NSCs may influence proper brain growth and structure.

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6

Schink, Kay O. y Harald Stenmark. "Cell Differentiation: Midbody Remnants — Junk or Fate Factors?" Current Biology 21, n.º 23 (diciembre de 2011): R958—R960. http://dx.doi.org/10.1016/j.cub.2011.10.035.

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7

Crowell, E. F., A. L. Gaffuri, B. Gayraud-Morel, S. Tajbakhsh y A. Echard. "Engulfment of the midbody remnant after cytokinesis in mammalian cells". Journal of Cell Science 127, n.º 17 (7 de julio de 2014): 3840–51. http://dx.doi.org/10.1242/jcs.154732.

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8

Casares-Arias, Javier, María Ujué González, Alvaro San Paulo, Leandro N. Ventimiglia, Jessica B. A. Sadler, David G. Miguez, Leticia Labat-de-Hoz et al. "Midbody Remnant Inheritance Is Regulated by the ESCRT Subunit CHMP4C". iScience 23, n.º 6 (junio de 2020): 101244. http://dx.doi.org/10.1016/j.isci.2020.101244.

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9

Khripkov, I. S. y A. A. Golikova. "The remnant of the midbody as a cellular signaling mechanism". Morphologia 18, n.º 1 (29 de abril de 2024): 19–25. http://dx.doi.org/10.26641/1997-9665.2024.1.19-25.

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Cell signaling mechanisms are the basis for intercellular integration and regulation of proliferation and differentiation processes at the systemic level. One of the most plausible ways to control cell-to-cell interaction and targeted distribution of genetic information is for cells to use their own structures that are formed during mitosis and carry RNA-dependent signaling molecules that affect the mechanisms of control of intercellular interaction, cell proliferation and differentiation. The midbody remnant is a microtubule-rich structure that forms between dividing cells in the last stages of cytokinesis. Previously, it was thought to be only a temporary structure of the intercellular bridge during cytokinesis, which served to connect two future daughter cells. This structure is a key regulator of abscission and functions as a signaling platform that coordinates the cytoskeleton and endosomal dynamics during the terminal stages of cell division. The midbody is a subcellular structure that is formed during cell division, during penetration into the cleavage sulcus, when the microtubules of the central spindle are compacted and cross-linked by a thin intracellular bridge connecting the two daughter cells. The midbody plays a key role in organizing cytokinesis by recruiting a variety of mitotic kinases such as Aurora B and Plk1, as well as sulcus endosomes containing Rab11/FIP3, the membrane-rupturing ESCRT complex and the microtubule-rupturing enzyme spastin, all of which are responsible for mediated rupture during the later stages of cytokinesis. The midbodies can serve as extracellular and intracellular polarity signals during early embryogenesis, as well as during epithelialization and polarization of neurons. The molecular mechanism that governs the positioning of the middle body and how it transmits signals to neurons during differentiation or epithelium remains unknown. Importantly, the remains of the middle bodies can also function as intracellular signaling scaffolds that regulate proliferation and fate postmitotic cells. Since these structures can be released outside cells and taken up by other non-mitotic cells, it is suggested that they may function as vehicles for alternative transmission of complex sets of signaling molecules and/or receptors between cells, thus profoundly affecting signaling in general.

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10

Crowell, Elizabeth Faris, Jean-Yves Tinevez y Arnaud Echard. "A simple model for the fate of the cytokinesis midbody remnant: Implications for remnant degradation by autophagy". BioEssays 35, n.º 5 (1 de marzo de 2013): 472–81. http://dx.doi.org/10.1002/bies.201200132.

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11

Boullé, Mikaël, Laurianne Davignon, Keïs Nabhane Saïd Halidi, Salomé Guez, Emilie Giraud, Marcel Hollenstein y Fabrice Agou. "High-Content RNAi Phenotypic Screening Unveils the Involvement of Human Ubiquitin-Related Enzymes in Late Cytokinesis". Cells 11, n.º 23 (30 de noviembre de 2022): 3862. http://dx.doi.org/10.3390/cells11233862.

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CEP55 is a central regulator of late cytokinesis and is overexpressed in numerous cancers. Its post-translationally controlled recruitment to the midbody is crucial to the structural coordination of the abscission sequence. Our recent evidence that CEP55 contains two ubiquitin-binding domains was the first structural and functional link between ubiquitin signaling and ESCRT-mediated severing of the intercellular bridge. So far, high-content screens focusing on cytokinesis have used multinucleation as the endpoint readout. Here, we report an automated image-based detection method of intercellular bridges, which we applied to further our understanding of late cytokinetic signaling by performing an RNAi screen of ubiquitin ligases and deubiquitinases. A secondary validation confirmed four candidate genes, i.e., LNX2, NEURL, UCHL1 and RNF157, whose downregulation variably affects interconnected phenotypes related to CEP55 and its UBDs, as follows: decreased recruitment of CEP55 to the midbody, increased number of midbody remnants per cell, and increased frequency of intercellular bridges or multinucleation events. This brings into question the Notch-dependent or independent contributions of LNX2 and NEURL proteins to late cytokinesis. Similarly, the role of UCHL1 in autophagy could link its function with the fate of midbody remnants. Beyond the biological interest, this high-content screening approach could also be used to isolate anticancer drugs that act by impairing cytokinesis and CEP55 functions.

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12

Goss, John W. y Derek K. Toomre. "Both daughter cells traffic and exocytose membrane at the cleavage furrow during mammalian cytokinesis". Journal of Cell Biology 181, n.º 7 (23 de junio de 2008): 1047–54. http://dx.doi.org/10.1083/jcb.200712137.

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Membrane trafficking during cytokinesis is not well understood. We used advanced live cell imaging techniques to track exocytosis of single vesicles to determine whether constitutively exocytosed membrane is focally delivered to the cleavage furrow. Ultrasensitive three-dimensional confocal time-lapse imaging of the temperature-sensitive membrane cargo protein vesicular stomatitis virus protein–yellow fluorescent protein revealed that vesicles from both daughter cells traffic out of the Golgi and into the furrow, following curvilinear paths. Immunolocalization and photobleaching experiments indicate that individual vesicles accumulate at the midbody and generate a reserve vesicle pool that is distinct from endosomal and lysosomal compartments. Total internal reflection fluorescence microscopy imaging provided direct evidence that Golgi-derived vesicles from both daughter cells not only traffic to the furrow region but dock and fuse there, supporting a symmetrically polarized exocytic delivery model. In contrast, quantitative analysis of midbody abscission showed inheritance of the midbody remnant by one daughter cell, indicating that cytokinesis is composed of both symmetrical and asymmetrical stages.

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13

Pinheiro, Diana y Yohanns Bellaïche. "Making the Most of the Midbody Remnant: Specification of the Dorsal-Ventral Axis". Developmental Cell 28, n.º 3 (febrero de 2014): 219–20. http://dx.doi.org/10.1016/j.devcel.2014.01.026.

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14

Presle, Adrien, Stéphane Frémont, Audrey Salles, Pierre-Henri Commere, Nathalie Sassoon, Clarisse Berlioz-Torrent, Neetu Gupta-Rossi y Arnaud Echard. "The viral restriction factor tetherin/BST2 tethers cytokinetic midbody remnants to the cell surface". Current Biology 31, n.º 10 (mayo de 2021): 2203–13. http://dx.doi.org/10.1016/j.cub.2021.02.039.

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15

Schumacher, Jill M., Andy Golden y Peter J. Donovan. "AIR-2: An Aurora/Ipl1-related Protein Kinase Associated with Chromosomes and Midbody Microtubules Is Required for Polar Body Extrusion and Cytokinesis in Caenorhabditis elegans Embryos". Journal of Cell Biology 143, n.º 6 (14 de diciembre de 1998): 1635–46. http://dx.doi.org/10.1083/jcb.143.6.1635.

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An emerging family of kinases related to the Drosophila Aurora and budding yeast Ipl1 proteins has been implicated in chromosome segregation and mitotic spindle formation in a number of organisms. Unlike other Aurora/Ipl1-related kinases, the Caenorhabditis elegans orthologue, AIR-2, is associated with meiotic and mitotic chromosomes. AIR-2 is initially localized to the chromosomes of the most mature prophase I–arrested oocyte residing next to the spermatheca. This localization is dependent on the presence of sperm in the spermatheca. After fertilization, AIR-2 remains associated with chromosomes during each meiotic division. However, during both meiotic anaphases, AIR-2 is present between the separating chromosomes. AIR-2 also remains associated with both extruded polar bodies. In the embryo, AIR-2 is found on metaphase chromosomes, moves to midbody microtubules at anaphase, and then persists at the cytokinesis remnant. Disruption of AIR-2 expression by RNA- mediated interference produces entire broods of one-cell embryos that have executed multiple cell cycles in the complete absence of cytokinesis. The embryos accumulate large amounts of DNA and microtubule asters. Polar bodies are not extruded, but remain in the embryo where they continue to replicate. The cytokinesis defect appears to be late in the cell cycle because transient cleavage furrows initiate at the proper location, but regress before the division is complete. Additionally, staining with a marker of midbody microtubules revealed that at least some of the components of the midbody are not well localized in the absence of AIR-2 activity. Our results suggest that during each meiotic and mitotic division, AIR-2 may coordinate the congression of metaphase chromosomes with the subsequent events of polar body extrusion and cytokinesis.

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16

Park, Sungjin, Smit A. Patel, Elizabeth E. Torr, Ashley-Grace N. Dureke, Alina M. McIntyre y Ahna R. Skop. "A protocol for isolating and imaging large extracellular vesicles or midbody remnants from mammalian cell culture". STAR Protocols 4, n.º 4 (diciembre de 2023): 102562. http://dx.doi.org/10.1016/j.xpro.2023.102562.

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17

Ou, Guangshuo, Christian Gentili y Pierre Gönczy. "Stereotyped distribution of midbody remnants in early C. elegans embryos requires cell death genes and is dispensable for development". Cell Research 24, n.º 2 (15 de octubre de 2013): 251–53. http://dx.doi.org/10.1038/cr.2013.140.

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18

LIMA, ALBERTINA P., JANALEE P. CALDWELL, GRAZIELA BIAVATI y ANELISE MONTANARIN. "A new species of Allobates (Anura: Aromobatidae) from Paleovárzea Forest in Amazonas, Brazil". Zootaxa 2337, n.º 1 (18 de enero de 2010): 1. http://dx.doi.org/10.11646/zootaxa.2337.1.1.

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Numerous species of aromobatid frogs in the genus Allobates from the Amazonian region of Brazil have been described in recent years. Herein, we describe a new Allobates from the state of Amazonas. This species is allopatric with three other species of Allobates, two of which we have described previously. The new species inhabits streams in small remnants of paleovárzea forest along margins of a small river, the Paraná do Castanho. Paleovárzeas are ancient floodplains of the Amazon River and its tributaries. Paleovárzea forests are transitional between terra firme forests, which are never flooded, and várzeas, which are seasonally flooded. Males and females of the new species are similar in size; males average 20.1 mm, females 19.8. Tadpoles have a distinct dark brown bar extending from the snout through the eye to midbody. The call of this species consists of quickly repeated groups of single notes and is unique compared to known species of Allobates. Courtship includes cephalic amplexus. Eggs are deposited on the forest floor in cup-shaped leaves in the litter. Unlike other species of Allobates, egg capsules in this species are opaque instead of clear.

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19

Zsidai, Bálint, Gian Andrea Lucidi, Philipp W. Winkler, Ryan J. Gnandt, Ian D. Engler y Volker Musahl. "All-Soft Tissue Meniscus Allograft Transplantation: Indications, Techniques, and Results". Video Journal of Sports Medicine 2, n.º 5 (septiembre de 2022): 263502542211070. http://dx.doi.org/10.1177/26350254221107036.

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Background: Meniscus allograft transplantation (MAT) may be indicated for young patients with joint line pain following subtotal or total meniscectomy. Several different approaches for performing MAT have been described in the literature and are influenced by appropriate patient selection, graft-sizing, and soft-tissue fixation techniques. Clinical studies demonstrate favorable results regarding pain relief and knee function in young patients undergoing MAT, making it a viable option for the treatment of postmeniscectomy syndrome. Indications: Meniscus allograft transplantation is indicated for symptomatic patients following subtotal or total meniscectomy. Selection criteria include patient age below 40 to 45 years, body mass index below 35, chondral changes of grade 2 or less, anatomic or correctable joint alignment, and normal or correctable knee stability. Technique Description: A standard arthroscopy is performed to confirm the indication for MAT, followed by debridement of the meniscus remnant up to the meniscus-capsular junction. The meniscus horns are prepared using a single No. 5 suture, while 4 to 5 No. 2 sutures are passed through the posterior body. The anterior and posterior root tunnels are drilled, and the meniscus is inserted through a posterior vertical arthrotomy using suture passers transmitted via the bone tunnels. The allograft is manipulated into proper position with a probe and the application of axial traction on the posterior root suture. At this point, sutures attached to the posterior horn are passed to the posterior capsule and 6 to 8 inside-out sutures are used to stabilize and fixate the midbody and anterior portion of the allograft. Results: Several clinical studies report good outcomes following MAT with a mean survival rate of approximately 70% at 10-year follow-up and 60% at 15 years. Additionally, some evidence is currently available regarding the long-term chondroprotective effect of MAT. Description/Conclusion: All-soft tissue meniscus allograft transplantation is a feasible approach for substitution of the damaged native meniscus and maintenance of tibiofemoral contact mechanics. Consequently, MAT is an important procedure in the toolkit of knee surgeons providing treatment for young, symptomatic postmeniscectomy patients.

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20

Jung, Gyu Ik, Daniela Londoño-Vásquez, Sungjin Park, Ahna R. Skop, Ahmed Z. Balboula y Karen Schindler. "An oocyte meiotic midbody cap is required for developmental competence in mice". Nature Communications 14, n.º 1 (16 de noviembre de 2023). http://dx.doi.org/10.1038/s41467-023-43288-x.

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AbstractEmbryo development depends upon maternally derived materials. Mammalian oocytes undergo extreme asymmetric cytokinesis events, producing one large egg and two small polar bodies. During cytokinesis in somatic cells, the midbody and subsequent assembly of the midbody remnant, a signaling organelle containing RNAs, transcription factors and translation machinery, is thought to influence cellular function or fate. The role of the midbody and midbody remnant in gametes, in particular, oocytes, remains unclear. Here, we examined the formation and function of meiotic midbodies (mMB) and mMB remnants using mouse oocytes and demonstrate that mMBs have a specialized cap structure that is orientated toward polar bodies. We show that that mMBs are translationally active, and that mMB caps are required to retain nascent proteins in eggs. We propose that this specialized mMB cap maintains genetic factors in eggs allowing for full developmental competency.

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21

Labat-de-Hoz, Leticia, Armando Rubio-Ramos, Javier Casares-Arias, Miguel Bernabé-Rubio, Isabel Correas y Miguel A. Alonso. "A Model for Primary Cilium Biogenesis by Polarized Epithelial Cells: Role of the Midbody Remnant and Associated Specialized Membranes". Frontiers in Cell and Developmental Biology 8 (7 de enero de 2021). http://dx.doi.org/10.3389/fcell.2020.622918.

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Primary cilia are solitary, microtubule-based protrusions surrounded by a ciliary membrane equipped with selected receptors that orchestrate important signaling pathways that control cell growth, differentiation, development and homeostasis. Depending on the cell type, primary cilium assembly takes place intracellularly or at the cell surface. The intracellular route has been the focus of research on primary cilium biogenesis, whereas the route that occurs at the cell surface, which we call the “alternative” route, has been much less thoroughly characterized. In this review, based on recent experimental evidence, we present a model of primary ciliogenesis by the alternative route in which the remnant of the midbody generated upon cytokinesis acquires compact membranes, that are involved in compartmentalization of biological membranes. The midbody remnant delivers part of those membranes to the centrosome in order to assemble the ciliary membrane, thereby licensing primary cilium formation. The midbody remnant's involvement in primary cilium formation, the regulation of its inheritance by the ESCRT machinery, and the assembly of the ciliary membrane from the membranes originally associated with the remnant are discussed in the context of the literature concerning the ciliary membrane, the emerging roles of the midbody remnant, the regulation of cytokinesis, and the role of membrane compartmentalization. We also present a model of cilium emergence during evolution, and summarize the directions for future research.

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22

Park, Sungjin, Randall Dahn, Elif Kurt, Adrien Presle, Kathryn VanDenHeuvel, Cara Moravec, Ashwini Jambhekar et al. "The mammalian midbody and midbody remnant are assembly sites for RNA and localized translation". Developmental Cell, agosto de 2023. http://dx.doi.org/10.1016/j.devcel.2023.07.009.

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23

Sardina, Francesca, Laura Monteonofrio, Manuela Ferrara, Fiorenza Magi, Silvia Soddu y Cinzia Rinaldo. "HIPK2 Is Required for Midbody Remnant Removal Through Autophagy-Mediated Degradation". Frontiers in Cell and Developmental Biology 8 (15 de septiembre de 2020). http://dx.doi.org/10.3389/fcell.2020.572094.

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24

McNeely, Katrina C. y Noelle D. Dwyer. "Cytokinetic Abscission Regulation in Neural Stem Cells and Tissue Development". Current Stem Cell Reports, 11 de agosto de 2021. http://dx.doi.org/10.1007/s40778-021-00193-7.

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Abstract Purpose of Review How stem cells balance proliferation with differentiation, giving rise to specific daughter cells during development to build an embryo or tissue, remains an open question. Here, we discuss recent evidence that cytokinetic abscission regulation in stem cells, particularly neural stem cells (NSCs), is part of the answer. Abscission is a multi-step process mediated by the midbody, a microtubule-based structure formed in the intercellular bridge between daughter cells after mitosis. Recent Findings Human mutations and mouse knockouts in abscission genes reveal that subtle disruptions of NSC abscission can cause brain malformations. Experiments in several epithelial systems have shown that midbodies serve as scaffolds for apical junction proteins and are positioned near apical membrane fate determinants. Abscission timing is tightly controlled and developmentally regulated in stem cells, with delayed abscission in early embryos and faster abscission later. Midbody remnants (MBRs) contain over 400 proteins and may influence polarity, fate, and ciliogenesis. Summary As NSCs and other stem cells build tissues, they tightly regulate three aspects of abscission: midbody positioning, duration, and MBR handling. Midbody positioning and remnants establish or maintain cell polarity. MBRs are deposited on the apical membranes of epithelia, can be released or internalized by surrounding cells, and may sequester fate determinants or transfer information between cells. Work in cell lines and simpler systems has shown multiple roles for abscission regulation influencing stem cell polarity, potency, and daughter fates during development. Elucidating how the abscission process influences cell fate and tissue growth is important for our continued understanding of brain development and stem cell biology.

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25

Rai, Alin, David W. Greening, Rong Xu, Maoshan Chen, Wittaya Suwakulsiri y Richard J. Simpson. "Secreted midbody remnants are a class of extracellular vesicles molecularly distinct from exosomes and microparticles". Communications Biology 4, n.º 1 (25 de marzo de 2021). http://dx.doi.org/10.1038/s42003-021-01882-z.

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AbstractDuring the final stages of cell division, newly-formed daughter cells remain connected by a thin intercellular bridge containing the midbody (MB), a microtubule-rich organelle responsible for cytokinetic abscission. Following cell division the MB is asymmetrically inherited by one daughter cell where it persists as a midbody remnant (MB-R). Accumulating evidence shows MB-Rs are secreted (sMB-Rs) into the extracellular medium and engulfed by neighbouring non-sister cells. While much is known about intracellular MB-Rs, sMB-Rs are poorly understood. Here, we report the large-scale purification and biochemical characterisation of sMB-Rs released from colon cancer cells, including profiling of their proteome using mass spectrometry. We show sMB-Rs are an abundant class of membrane-encapsulated extracellular vesicle (200-600 nm) enriched in core cytokinetic proteins and molecularly distinct from exosomes and microparticles. Functional dissection of sMB-Rs demonstrated that they are engulfed by, and accumulate in, quiescent fibroblasts where they promote cellular transformation and an invasive phenotype.

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26

LI, Zhengyang, Lianshun LI, Huiming ZHAO, Subing LI, Wengui SHI y Zuoyi JIAO. "Midbody remnant regulates the formation of primary cilia and its relation with tumorigenesis and tumor progression". Journal of Zhejiang University (Medical Sciences), 1 de febrero de 2024. http://dx.doi.org/10.3724/zdxbyxb-2023-0461.

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27

Suwakulsiri, Wittaya, Rong Xu, Alin Rai, Adnan Shafiq, Maoshan Chen, David W. Greening y Richard J. Simpson. "Comparative proteomic analysis of three major extracellular vesicle classes secreted from human primary and metastatic colorectal cancer cells: Exosomes, microparticles, and shed midbody remnants". PROTEOMICS, 28 de julio de 2023. http://dx.doi.org/10.1002/pmic.202300057.

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AbstractCell‐derived extracellular vesicles (EVs) are evolutionary‐conserved secretory organelles that, based on their molecular composition, are important intercellular signaling regulators. At least three classes of circulating EVs are known based on mechanism of biogenesis: exosomes (sEVs/Exos), microparticles (lEVs/MPs), and shed midbody remnants (lEVs/sMB‐Rs). sEVs/Exos are of endosomal pathway origin, microparticles (lEVs/MPs) from plasma membrane blebbing and shed midbody remnants (lEVs/sMB‐Rs) arise from symmetric cytokinetic abscission. Here, we isolate sEVs/Exos, lEVs/MPs, and lEVs/sMB‐Rs secreted from human isogenic primary (SW480) and metastatic (SW620) colorectal cancer (CRC) cell lines in milligram quantities for label‐free MS/MS‐based proteomic profiling. Purified EVs revealed selective composition packaging of exosomal protein markers in SW480/SW620‐sEVs/Exos, metabolic enzymes in SW480/SW620‐lEVs/MPs, while centralspindlin complex proteins, nucleoproteins, splicing factors, RNA granule proteins, translation‐initiation factors, and mitochondrial proteins selectively traffic to SW480/SW620‐ lEVs/sMB‐Rs. Collectively, we identify 39 human cancer‐associated genes in EVs; 17 associated with SW480‐EVs, 22 with SW620‐EVs. We highlight oncogenic receptors/transporters selectively enriched in sEVs/Exos (EGFR/FAS in SW480‐sEVs/Exos and MET, TGFBR2, ABCB1 in SW620‐sEVs/Exos). Interestingly, MDK, STAT1, and TGM2 are selectively enriched in SW480‐lEVs/sMB‐Rs, and ADAM15 to SW620‐lEVs/sMB‐Rs. Our study reveals sEVs/Exos, lEVs/MPs, and lEVs/sMB‐Rs have distinct protein signatures that open potential diagnostic avenues of distinct types of EVs for clinical utility.

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Bernabé-Rubio, Miguel, David Gershlick y Miguel Alonso. "Physical Removal of the Midbody Remnant from Polarised Epithelial Cells Using Take-Up by Suction Pressure (TUSP)". BIO-PROTOCOL 7, n.º 8 (2017). http://dx.doi.org/10.21769/bioprotoc.2244.

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Suwakulsiri, Wittaya, Rong Xu, Alin Rai, Maoshan Chen, Adnan Shafiq, David W. Greening y Richard J. Simpson. "Transcriptomic analysis and fusion gene identifications of midbody remnants released from colorectal cancer cells reveals they are molecularly distinct from exosomes and microparticles". PROTEOMICS, 12 de marzo de 2024. http://dx.doi.org/10.1002/pmic.202300058.

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AbstractPreviously, we reported that human primary (SW480) and metastatic (SW620) colorectal (CRC) cells release three classes of membrane‐encapsulated extracellular vesicles (EVs); midbody remnants (MBRs), exosomes (Exos), and microparticles (MPs). We reported that MBRs were molecularly distinct at the protein level. To gain further biochemical insights into MBRs, Exos, and MPs and their emerging role in CRC, we performed, and report here, for the first time, a comprehensive transcriptome and long noncoding RNA sequencing analysis and fusion gene identification of these three EV classes using the next‐generation RNA sequencing technique. Differential transcript expression analysis revealed that MBRs have a distinct transcriptomic profile compared to Exos and MPs with a high enrichment of mitochondrial transcripts lncRNA/pseudogene transcripts that are predicted to bind to ribonucleoprotein complexes, spliceosome, and RNA/stress granule proteins. A salient finding from this study is a high enrichment of several fusion genes in MBRs compared to Exos, MPs, and cell lysates from their parental cells such as MSH2 (gene encoded DNA mismatch repair protein MSH2). This suggests potential EV‐liquid biopsy targets for cancer detection. Importantly, the expression of cancer progression‐related transcripts found in EV classes derived from SW480 (EGFR) and SW620 (MET and MACCA1) cell lines reflects their parental cell types. Our study is the report of RNA and fusion gene compositions within MBRs (including Exos and MPs) that could have an impact on EV functionality in cancer progression and detection using EV‐based RNA/ fusion gene candidates for cancer biomarkers.

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