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Artículos de revistas sobre el tema "Connexome"

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Autor: Grafiati

Publicado: 13 de abril de 2024

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1

Sykora, Matus, Katarina Andelova, Barbara Szeiffova Bacova, Tamara Egan Benova, Adriana Martiskova, Vladimir Knezl y Narcis Tribulova. "Hypertension Induces Pro-arrhythmic Cardiac Connexome Disorders: Protective Effects of Treatment". Biomolecules 13, n.º 2 (9 de febrero de 2023): 330. http://dx.doi.org/10.3390/biom13020330.

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Prolonged population aging and unhealthy lifestyles contribute to the progressive prevalence of arterial hypertension. This is accompanied by low-grade inflammation and over time results in heart dysfunction and failure. Hypertension-induced myocardial structural and ion channel remodeling facilitates the development of both atrial and ventricular fibrillation, and these increase the risk of stroke and sudden death. Herein, we elucidate hypertension-induced impairment of “connexome” cardiomyocyte junctions. This complex ensures cell-to-cell adhesion and coupling for electrical and molecular signal propagation. Connexome dysfunction can be a key factor in promoting the occurrence of both cardiac arrhythmias and heart failure. However, the available literature indicates that arterial hypertension treatment can hamper myocardial structural remodeling, hypertrophy and/or fibrosis, and preserve connexome function. This suggests the pleiotropic effects of antihypertensive agents, including anti-inflammatory. Therefore, further research is required to identify specific molecular targets and pathways that will protect connexomes, and it is also necessary to develop new approaches to maintain heart function in patients suffering from primary or pulmonary arterial hypertension.

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2

Agullo-Pascual, Esperanza, Marina Cerrone y Mario Delmar. "Arrhythmogenic cardiomyopathy and Brugada syndrome: Diseases of the connexome". FEBS Letters 588, n.º 8 (15 de febrero de 2014): 1322–30. http://dx.doi.org/10.1016/j.febslet.2014.02.008.

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3

Sala, Gabriele, Salvatore Badalamenti y Claudio Ponticelli. "The Renal Connexome and Possible Roles of Connexins in Kidney Diseases". American Journal of Kidney Diseases 67, n.º 4 (abril de 2016): 677–87. http://dx.doi.org/10.1053/j.ajkd.2015.09.030.

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4

Leo-Macias, Alejandra, Esperanza Agullo-Pascual y Mario Delmar. "The cardiac connexome: Non-canonical functions of connexin43 and their role in cardiac arrhythmias". Seminars in Cell & Developmental Biology 50 (febrero de 2016): 13–21. http://dx.doi.org/10.1016/j.semcdb.2015.12.002.

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5

Agullo-Pascual, Esperanza, Dylan A. Reid, Sarah Keegan, Manavjeet Sidhu, David Fenyö, Eli Rothenberg y Mario Delmar. "Super-resolution fluorescence microscopy of the cardiac connexome reveals plakophilin-2 inside the connexin43 plaque". Cardiovascular Research 100, n.º 2 (8 de agosto de 2013): 231–40. http://dx.doi.org/10.1093/cvr/cvt191.

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6

Chen-Izu, Ye, Alonso P. Moreno y Robert A. Spangler. "Opposing gates model for voltage gating of gap junction channels". American Journal of Physiology-Cell Physiology 281, n.º 5 (1 de noviembre de 2001): C1604—C1613. http://dx.doi.org/10.1152/ajpcell.2001.281.5.c1604.

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Gap junctions are intercellular channels that link the cytoplasm of neighboring cells. Because a gap junction channel is composed of two connexons docking head-to-head with each other, the channel voltage-gating profile is symmetrical for homotypic channels made of two identical connexons (hemichannels) and asymmetric for the heterotypic channels made of two different connexons (i.e., different connexin composition). In this study we have developed a gating model that allows quantitative characterization of the voltage gating of homotypic and heterotypic channels. This model differs from the present model in use by integrating, rather than separating, the contributions of the voltage gates of the two member connexons. The gating profile can now be fitted over the entire voltage range, eliminating the previous need for data splicing and fusion of two hemichannel descriptions, which is problematic when dealing with heterotypic channels. This model also provides a practical formula to render quantitative several previously qualitative concepts, including a similarity principle for matching a voltage gate to its host connexon, assignment of gating polarity to a connexon, and the effect of docking interactions between two member connexons in an intact gap junction channel.

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7

Hand, G., V. Nguyen, K. Downing, D. Mueller, A. Engel, Bruce Nicholson y G. Sosinsky. "Isolation and Characterization of Connexin26 Gap Junctions from Transfected Hela Cells". Microscopy and Microanalysis 6, S2 (agosto de 2000): 246–47. http://dx.doi.org/10.1017/s1431927600033729.

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Gap junctions are composed of a multigene family of proteins called the connexins with a similar sequence and folding topology. Connexons, half-channels made from a particular connexin, will dock and form functional channels with some, but not all, connexons made of other isoforms. This is surprising considering that the primary sequences of the docking domains are conserved and in some cases there are limited amino acid changes in the extracellular loops between compatible connexins. Therefore, some tertiary or quaternary interactions between the extracellular loops of the two docking hemichannels must contribute to the compatibility of a connexon assembled from one connexin for a connexon made from a different connexin. The 3D structures of gap junctions composed of only three isoforms have been investigated with only one case of a gap junction structure at better than 1 nm resolution [1]. The rat liver hemichannel structure is the only one that contains an exposed extracellular surface [2].

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8

Perkins, Guy, Dan Goodenough y Gina Sosinsky. "Three-Dimensional Structure of the Gap Junction Connexon and Intercellular Channel". Microscopy and Microanalysis 3, S2 (agosto de 1997): 227–28. http://dx.doi.org/10.1017/s1431927600008023.

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Gap junctions are specialized cell-cell contact areas by which cells communication with each other. Within these contact areas are tens to thousands of membrane channels. A gap junction membrane channel (also referred to as an intercellular channel) is unique among membrane channels in that it is composed of two oligomers with each of two adjacent tissue cells contributing one oligomer (called a connexon or hemichannel). The pore of the intercellular channel controls the passage of small molecules and ions from one cell to another.We are interested in how the structure and surface topology of the gap junction connexon at its extracellular surface influences the docking and formation of an intercellular communicating channel. It has been demonstrated that connexons made from some connexins will dock and form functional channels with some but not all connexons made from other isoforms. This selectivity is surprising considering that the primary sequences of the docking domains are highly conserved.

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9

Garcia-Niebla, Javier, Andrés Ricardo Pérez-Riera, Rodrigo de Souza Abreu, Raimundo Barbosa-Barros, Díaz Muñoz y Kjell Nikus. "Brugada syndrome unmasked by fever and paradoxical lower degree of dromotropic disturbance in the right ventricular outflow tract". Journal of Human Growth and Development 32, n.º 2 (23 de junio de 2022): 187–91. http://dx.doi.org/10.36311/jhgd.v32.13319.

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Brugada syndrome (BrS) is an inherited clinical-electrocardiographic arrhythmic entity with an autosomal dominant genetic pattern of inheritance or de novo variant. The syndrome has low worldwide prevalence, but is endemic in Southeast Asian countries (Thailand, Philippines and Japan). The BrS is a subtle structural heart disease (SHD), and the diagnosis is only possible when the so-called type 1 Brugada ECG pattern is spontaneously present or induced for example with fever. Repolarization-depolarization disturbances in BrS patients can be caused by genetic mutations, abnormal neural crest cell migration, low expression of connexin-43 gap junction protein, or connexome disturbances. A recent autopsy study revealed increase in biventricular collagen with myocardial fibrosis when compared with control subjects although the main affected cardiac territory is the right ventricular outflow tract (RVOT). In this location, there is abnormally low expression of significant connexin-43 gap junction responsible for the electro-vectorcardiographic manifestations of terminal QRS conduction delay in the right standard precordial leads (V1-V2), high right precordial leads (V1H-V2H), as well as in the unipolar aVR lead (“the forgotten lead”). Based on their location, these leads reflect the electrical activity of the RVOT.

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10

Rhett, J. Matthew, Jane Jourdan y Robert G. Gourdie. "Connexin 43 connexon to gap junction transition is regulated by zonula occludens-1". Molecular Biology of the Cell 22, n.º 9 (mayo de 2011): 1516–28. http://dx.doi.org/10.1091/mbc.e10-06-0548.

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Connexin 43 (Cx43) is a gap junction (GJ) protein widely expressed in mammalian tissues that mediates cell-to-cell coupling. Intercellular channels comprising GJ aggregates form from docking of paired connexons, with one each contributed by apposing cells. Zonula occludens-1 (ZO-1) binds the carboxy terminus of Cx43, and we have previously shown that inhibition of the Cx43/ZO-1 interaction increases GJ size by 48 h. Here we demonstrated that increases in GJ aggregation occur within 2 h (∼Cx43 half-life) following disruption of Cx43/ZO-1. Immunoprecipitation and Duolink protein–protein interaction assays indicated that inhibition targets ZO-1 binding with Cx43 in GJs as well as connexons in an adjacent domain that we term the “perinexus.” Consistent with GJ size increases being matched by decreases in connexons, inhibition of Cx43/ZO-1 reduced the extent of perinexal interaction, increased the proportion of connexons docked in GJs relative to undocked connexons in the plasma membrane, and increased GJ intercellular communication while concomitantly decreasing hemichannel-mediated membrane permeance in contacting, but not noncontacting, cells. ZO-1 small interfering RNA and overexpression experiments verified that loss and gain of ZO-1 function govern the transition of connexons into GJs. It is concluded that ZO-1 regulates the rate of undocked connexon aggregation into GJs, enabling dynamic partitioning of Cx43 channel function between junctional and proximal nonjunctional domains of plasma membrane.

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11

Sosinsky, Gina, Maryann Martone, Galen Handel, Linda Musil y Mark Ellisman. "Correlative Confocal and Electron Microscopy of the Connexin43 Gap Junction Protein in NRK Cells: Balancing Fixation Conditions, Cell Permeabilization, Antigen-Antibody Interaction and Cell Ultrastructure." Microscopy and Microanalysis 4, S2 (julio de 1998): 450–51. http://dx.doi.org/10.1017/s1431927600022376.

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Synthesis and assembly of gap junction proteins into intercellular channels is an important biological problem with direct bearing on embryonic development. In particular, transgenic mice Cx43 gap junction protein knock-outs 1 and mutations in Cx43 sequence in human Viscera Hyper Taxia patients result in severely deformed hearts.NRK cells are one of the best studied systems for gap junction synthesis, transport and assembly. Gap junctions contain numerous cell-cell channels which are composed of two paired oligomers (called a connexon or hemichannel) each contributed from the plasma membrane of apposing cells. Although biochemical studies have shown indirectly that unpaired Cx43 connexons are in the plasma membrane, direct hemichannel visualization has not been demonstrated. Musil and Goodenough have shown that oligomerization occurs in the trans-Golgi network and the connexon is transported to the plasma membrane.

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12

Kistler, J., K. Goldie, P. Donaldson y A. Engel. "Reconstitution of native-type noncrystalline lens fiber gap junctions from isolated hemichannels." Journal of Cell Biology 126, n.º 4 (15 de agosto de 1994): 1047–58. http://dx.doi.org/10.1083/jcb.126.4.1047.

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Gap junctions contain numerous channels that are clustered in apposed membrane patches of adjacent cells. These cell-to-cell channels are formed by pairing of two hemichannels or connexons, and are also referred to as connexon pairs. We have investigated various detergents for their ability to separately solubilize hemichannels or connexon pairs from isolated ovine lens fiber membranes. The solubilized preparations were reconstituted with lipids with the aim to reassemble native-type gap junctions and to provide a model system for the characterization of the molecular interactions involved in this process. While small gap junction structures were obtained under a variety of conditions, large native-type gap junctions were assembled using a novel two-step procedure: in the first step, hemichannels that had been solubilized with octylpolyoxyethylene formed connexon pairs by dialysis against n-decyl-beta-D-maltopyranoside. In the second step, connexon pairs were reconstituted with phosphatidylcholines by dialysis against buffer containing Mg2+. This way, double-layered gap junctions with diameter < or = 300 nm were obtained. Up to several hundred channels were packed in a noncrystalline arrangement, giving these reconstituted gap junctions an appearance that was indistinguishable from that of the gap junctions in the lens fiber membranes.

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13

Leo-Macias, A., F. Liang y M. Delmar. "3D Tomographic Segmentation of Adult Cardiac Ventricle reveals a Complex Tubular and Vesicular Network surrounding the Gap Junction Plaque. Ultrastructure of the Connexome". Heart Rhythm 10, n.º 11 (noviembre de 2013): 1749–50. http://dx.doi.org/10.1016/j.hrthm.2013.09.078.

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14

Bao, Xiaoyong, Luis Reuss y Guillermo A. Altenberg. "Regulation of Purified and Reconstituted Connexin 43 Hemichannels by Protein Kinase C-mediated Phosphorylation of Serine 368". Journal of Biological Chemistry 279, n.º 19 (17 de febrero de 2004): 20058–66. http://dx.doi.org/10.1074/jbc.m311137200.

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Indirect evidence suggests that the permeability of connexin 43 (Cx43) gap-junctional channels (connexons) to small organic molecules (Mr< 1,000) is decreased by protein kinase C (PKC)-mediated phosphorylation of Ser-368. However, it is currently unknown whether this effect is produced directly by phosphorylation of this residue or whether cytoplasmic regulatory factors are required for the decrease in Cx43 gap-junctional channel permeability. Here we studied the effects of PKC-mediated phosphorylation on purified recombinant wild-type Cx43 and a PKC-unresponsive mutant (S368A). Our studies show that (a) PKC phosphorylates Ser-368, (b) the phosphorylation by PKC of purified and reconstituted connexons abolishes sucrose and Lucifer Yellow permeability, (c) the regulation of Cx43 by PKC is the direct result of phosphorylation of Ser-368 and does not involve intermediary regulatory factors, and (d) phosphorylation of Ser-368 produces a conformational change in purified Cx43 as demonstrated by changes in intrinsic Trp fluorescence and proteolytic digestion pattern. We conclude that phosphorylation of Ser-368 by PKC induces a conformational change of Cx43 that results in a decrease in connexon permeability.

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15

Birkenhäger, Ralf, Nicola Prera, Antje Aschendorff, Roland Laszig y Susan Arndt. "A Novel Homozygous Mutation in the EC1/EC2 Interaction Domain of the Gap Junction Complex Connexon 26 Leads to Profound Hearing Impairment". BioMed Research International 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/307976.

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To date, about 165 genetic loci or genes have been identified which are associated with nonsyndromal hearing impairment. In about half the cases, genetic defects in theGJB2gene (connexin 26) are the most common cause of inner-ear deafness. The genesGJB2andGJB6are localized on chromosome 13q11-12 in tandem orientation. Connexins belong to the group of “gap junction” proteins, which form connexons, each consisting of six connexin molecules. These are responsible for the exchange of ions and smaller molecules between neighboring cells. Mutational analysis in genesGJB2andGJB6was brought by direct sequencing of the coding exons including the intron transitions. Here we show in the participating extended family a homozygous mutation c.506G>A, (TGC>TAC) p.Cys169Tyr, in theGJB2gene, which could be proven for the first time and led to nonsyndromal severe hearing impairment in the afflicted patients. The mutation is located in the EC1/EC2 interaction complex of the gap junction connexon 26 complex and interrupts the K+circulation and therefore the ion homeostasis in the inner ear. The homozygous mutation p.Cys169Tyr identified here provides a novel insight into the structure-function relationship of the gap junction complex connexin/connexon 26.

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16

Héja, László, Ágnes Simon, Zsolt Szabó y Julianna Kardos. "Connexons Coupling to Gap Junction Channel: Potential Role for Extracellular Protein Stabilization Centers". Biomolecules 12, n.º 1 (30 de diciembre de 2021): 49. http://dx.doi.org/10.3390/biom12010049.

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Connexin (Cx) proteins establish intercellular gap junction channels (Cx GJCs) through coupling of two apposed hexameric Cx hemichannels (Cx HCs, connexons). Pre- and post-GJ interfaces consist of extracellular EL1 and EL2 loops, each with three conserved cysteines. Previously, we reported that known peptide inhibitors, mimicking a variety of Cx43 sequences, appear non-selective when binding to homomeric Cx43 vs. Cx36 GJC homology model subtypes. In pursuit of finding potentially Cx subtype-specific inhibitors of connexon-connexon coupling, we aimed at to understand better how the GJ interface is formed. Here we report on the discovery of Cx GJC subtype-specific protein stabilization centers (SCs) featuring GJ interface architecture. First, the Cx43 GJC homology model, embedded in two opposed membrane bilayers, has been devised. Next, we endorsed the fluctuation dynamics of SCs of the interface domain of Cx43 GJC by applying standard molecular dynamics under open and closed cystine disulfide bond (CS-SC) preconditions. The simulations confirmed the major role of the unique trans-GJ SC pattern comprising conserved (55N, 56T) and non-conserved (57Q) residues of the apposed EL1 loops in the stabilization of the GJC complex. Importantly, clusters of SC patterns residing close to the GJ interface domain appear to orient the interface formation via the numerous SCs between EL1 and EL2. These include central 54CS-S198C or 61CS-S192C contacts with residues 53R, 54C, 55N, 197D, 199F or 64V, 191P, respectively. In addition, we revealed that GJC interface formation is favoured when the psi dihedral angle of the nearby 193P residue is stable around 180° and the interface SCs disappear when this angle moves to the 0° to −45° range. The potential of the association of non-conserved residues with SC motifs in connexon-connexon coupling makes the development of Cx subtype-specific inhibitors viable.

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17

Hautefort, Aurélie, Anna Pfenniger y Brenda R. Kwak. "Endothelial connexins in vascular function". Vascular Biology 1, n.º 1 (3 de diciembre de 2019): H117—H124. http://dx.doi.org/10.1530/vb-19-0015.

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Gap junctions are essential for intercellular crosstalk in blood and lymphatic vasculature. These clusters of intercellular channels ensure direct communication among endothelial cells and between endothelial and smooth muscle cells, and the synchronization of their behavior along the vascular tree. Gap junction channels are formed by connexins; six connexins form a connexon or hemichannel and the docking of two connexons result in a full gap junction channel allowing for the exchange of ions and small metabolites between neighboring cells. Recent evidence indicates that the intracellular domains of connexins may also function as an interaction platform (interactome) for other proteins, thereby regulating their function. Interestingly, fragments of Cx proteins generated by alternative internal translation were recently described, although their functions in the vascular wall remain to be uncovered. Variations in connexin expression are observed along different types of blood and lymphatic vessels; the most commonly found endothelial connexins are Cx37, Cx40, Cx43 and Cx47. Physiological studies on connexin-knockout mice demonstrated the essential roles of these channel-forming proteins in the coordination of vasomotor activity, endothelial permeability and inflammation, angiogenesis and in the maintenance of fluid balance in the body.

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18

McCall, S. "Connexive Gentzen". Logic Journal of IGPL 22, n.º 6 (4 de julio de 2014): 964–81. http://dx.doi.org/10.1093/jigpal/jzu019.

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19

Günther, Mario. "A Connexive Conditional". Logos & Episteme 13, n.º 1 (2022): 55–63. http://dx.doi.org/10.5840/logos-episteme20221313.

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20

Francez, Nissim. "Connexive Restricted Quantification". Notre Dame Journal of Formal Logic 61, n.º 3 (septiembre de 2020): 383–402. http://dx.doi.org/10.1215/00294527-2020-0015.

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21

Francez, Nissim. "Bilateral Connexive Logic". Logics 1, n.º 3 (4 de agosto de 2023): 157–62. http://dx.doi.org/10.3390/logics1030008.

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This paper proposes a bilateral analysis of connexivity, presenting a bilateral natural deduction system for a weak connexive logic. The proposed logic deviates from other connexive logics and other bilateral logics in the following respects: (1) The logic induces a difference in meaning between inner and outer occurrences of negation in the connexive axioms. (2) The logic allows incoherence—assertion and denial of the same formula—while still being non-trivial.

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22

Sosinsky, Gina E. "Diversity in gap junction structures". Proceedings, annual meeting, Electron Microscopy Society of America 50, n.º 1 (agosto de 1992): 442–43. http://dx.doi.org/10.1017/s0424820100122617.

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Gap junctions are the specialized regions between two adjoining cells responsible for regulated communication. The morphological unit of the gap junction is composed of 12 copies of the connexin molecule. Six connexins form a hexamer in each cell membrane called a connexon and two connexons pair across the two cell membranes of coupled cells to form gated channels. Although other proteins are found in enriched gap junction preparations, it is generally accepted that the gap junction structures are formed from a family of connexin proteins. The connexins are named according to their DNA deduced molecular weights, e.g. Cx32 for the 32kDa liver major connexin and Cx26 for the 26 kDa liver minor connexin. Within a given tissue, several connexins are often found and different connexins are often found within the same junctional plaque. These connexins contain both conserved and variable domains in their primary amino acid sequences, with the major differences occuring in the sequence and size of the cytoplasmic C terminus. The most conserved regions of the compared sequences are in the transmembrane and gap portions of the proteins. Determination of the sequences of the connexin proteins and correlation of information on antibody binding, proteolytic cleavage and chemical reactivity have led to a model where the C- and N- termini are located at the cytoplasmc surface and four α-helical segments of the protein cross the membrane.

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23

Miller, T. M. y D. A. Goodenough. "Gap junction structures after experimental alteration of junctional channel conductance." Journal of Cell Biology 101, n.º 5 (1 de noviembre de 1985): 1741–48. http://dx.doi.org/10.1083/jcb.101.5.1741.

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Gap junctions are known to present a variety of different morphologies in electron micrographs and x-ray diffraction patterns. This variation in structure is not only seen between gap junctions in different tissues and organisms, but also within a given tissue. In an attempt to understand the physiological meaning of some aspects of this variability, gap junction structure was studied following experimental manipulation of junctional channel conductance. Both physiological and morphological experiments were performed on gap junctions joining stage 20-23 chick embryo lens epithelial cells. Channel conductance was experimentally altered by using five different experimental manipulations, and assayed for conductance changes by observing the intercellular diffusion of Lucifer Yellow CH. All structural measurements were made on electron micrographs of freeze-fracture replicas after quick-freezing of specimens from the living state; for comparison, aldehyde-fixed specimens were measured as well. Analysis of the data generated as a result of this study revealed no common statistically significant changes in the intrajunctional packing of connexons in the membrane plane as a result of experimental alteration of junctional channel conductance, although some of the experimental manipulations used to alter junctional conductance did produce significant structural changes. Aldehyde fixation caused a dramatic condensation of connexon packing, a result not observed with any of the five experimental uncoupling conditions over the 40-min time course of the experiments.

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24

Manjunath, C. K. y E. Page. "Cell biology and protein composition of cardiac gap junctions". American Journal of Physiology-Heart and Circulatory Physiology 248, n.º 6 (1 de junio de 1985): H783—H791. http://dx.doi.org/10.1152/ajpheart.1985.248.6.h783.

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The gap junctions that electrically couple mammalian myocardial cells have high (12,000–17,000/micron2)surface densities of channel-containing elements (connexons), undulating surfaces, and approximately hexagonally arrayed connexons disposed in small domains rotated with respect to one another. Optical diffraction combined with image processing of negatively stained isolated rabbit heart gap junctions shows six protein subunits surrounding the cell-to-cell channel and suggestive (but not conclusive) evidence for protein connections between connexons. Biochemical studies indicate that the six identical relative molecular weight (Mr) 47,000 subunits of mammalian cardiac gap junctions differ from liver gap junctions in the presence of a covalently bound Mr 17,500 cytoplasmic surface component that can be visualized electron microscopically in thin-sectioned and freeze-etched hearts. The cytoplasmic surface component is susceptible to cleavage by an alkaline serine protease released from mast cell granules by high ionic strength solutions (0.6 M KI) used to extract myofibrils during gap junction purification. Interlocking of connexons from coupled cells in the gap involves hydrogen bonding between protein subunits of the connexons.

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25

Jordan, K., R. Chodock, A. R. Hand y D. W. Laird. "The origin of annular junctions: a mechanism of gap junction internalization". Journal of Cell Science 114, n.º 4 (15 de febrero de 2001): 763–73. http://dx.doi.org/10.1242/jcs.114.4.763.

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Gap junctional intercellular communication is established when connexin proteins oligomerize into connexon hemichannels, which then pair at the cell surface with connexons from neighboring cells to form functional gap junction channels. Gap junction channels routinely cluster into gap junction plaques, which can exhibit dynamic characteristics while under the frequent processes of formation and removal from the cell surface. We have three lines of evidence to suggest that one mechanism of gap junction removal occurs when one of two contacting cells internalizes the gap junction contribution from both cells. First, in coculture experiments, green fluorescent protein-tagged connexin43 (Cx43-GFP) expressed in normal rat kidney (NRK) cells can be internalized into contacting cells that do not express Cx43-GFP, and the incidences of identifying these internalized structures increase in the presence of lysosomal inhibitors. Secondly, time-lapse imaging of live NRK cells revealed that large areas of gap junction plaques containing Cx43-GFP were internalized as vesicular-like structures into one of two adjacent cells. Finally, when live NRK cells that express endogenous Cx43 were microinjected with anti-Cx43 antibodies, antibody-tagged gap junctions were visualized in cells that contacted the microinjected cell within 3–6.5 hours. Together our results strongly suggest that one mechanism of gap junction removal from the cell surface involves a unique process in which the entire gap junction or a fragment of it is internalized into one of the two contacting cells as an annular junction.

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26

Ebihara, Lisa. "New Roles for Connexons". Physiology 18, n.º 3 (junio de 2003): 100–103. http://dx.doi.org/10.1152/nips.01431.2002.

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Connexons or gap junction hemichannels are large, nonselective ion channels that reside in the nonjunctional plasma membrane before their assembly into gap junction channels. Increasing evidence suggests that these channels can open under certain conditions and may participate in a number of cellular processes, including the release of small metabolites such as ATP and NAD+, which are involved in paracrine signaling.

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27

Hülser, Dieter F., Marie-Louise Rütz, Reiner Eckert y Otto Traub. "Functional rescue of defective mutant connexons by pairing with wild-type connexons". Pfl�gers Archiv European Journal of Physiology 441, n.º 4 (15 de enero de 2001): 521–28. http://dx.doi.org/10.1007/s004240000460.

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AHMAD, Shoeb, Juan A. DIEZ, Christopher H. GEORGE y W. Howard EVANS. "Synthesis and assembly of connexins in vitro into homomeric and heteromeric functional gap junction hemichannels". Biochemical Journal 339, n.º 2 (8 de abril de 1999): 247–53. http://dx.doi.org/10.1042/bj3390247.

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The biogenesis of connexins and their assembly into functional gap junction hemichannels (connexons) was studied with the use of a cell-free transcription/translation system. Velocity sedimentation on sucrose gradients showed that a small proportion of connexin (Cx) 26 and Cx32 that were co-translationally translocated into microsomes were oligomers of Cx26 and Cx32. Chemical cross-linking studies showed that these corresponded to hexameric connexons. Reconstitution of connexons synthesized in vitro into liposomes induced permeability properties consistent with the view that open gap junction hemichannels were produced. By using an immunoprecipitation approach, a simultaneous translation of Cx26 and Cx32 incorporated into microsomes resulted in homomeric connexons. However, supplementation of the translation system in vitro with liver Golgi membranes produced heteromeric connexons constructed of Cx32 and Cx26, and also resulted in an increased oligomerization especially of Cx32. All of the connexins analysed were inserted co-translationally into canine pancreatic microsomal membranes. In addition, Cx26 and Cx43, but not Cx32, were also inserted into microsomal membranes post-translationally. Analysis of various connexin constructs in which the cytoplasmic carboxy tails were transposed, the cytoplasmic tail of Cx43 was truncated or a reporter protein, aequorin, was attached to the C-terminus showed that tail length was not the major determinant of the post-translational membrane insertion of connexins.

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29

Szmuc, Damián. "Inferentialism and Relevance". Análisis Filosófico 41, n.º 2 (1 de noviembre de 2021): 317–36. http://dx.doi.org/10.36446/af.2021.458.

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This paper provides an inferentialist motivation for a logic belonging in the connexive family, by borrowing elements from the bilateralist interpretation for Classical Logic without the Cut rule, proposed by David Ripley. The paper focuses on the relation between inferentialism and relevance, through the exploration of what we call relevant assertion and denial, showing that a connexive system emerges as a symptom of this interesting link. With the present attempt we hope to broaden the available interpretations for connexive logics, showing they can be rightfully motivated in terms of certain relevantist constraints imposed on assertion and denial.

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30

Kirichenko, E. Yu, S. N. Skatchkov y A. M. Ermakov. "Structure and Functions of Gap Junctions and Their Constituent Connexins in the Mammalian CNS". Biochemistry (Moscow), Supplement Series A: Membrane and Cell Biology 15, n.º 2 (abril de 2021): 107–19. http://dx.doi.org/10.1134/s1990747821020069.

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Abstract— Numerous data obtained in the last 20 years indicate that all parts of the mature central nervous system, from the retina and olfactory bulb to the spinal cord and brain, contain cells connected by gap junctions (GJs). The morphological basis of the GJs is a group of joined membrane hemichannels called connexons, the subunit of each connexon is the protein connexin. In the central nervous system, connexins show specificity and certain types of them are expressed either in neurons or in glial cells. Connexins and GJs of neurons, combining certain types of inhibitory hippocampal and neocortical neuronal ensembles, provide synchronization of local impulse and rhythmic activity, thalamocortical conduction, control of excitatory connections, which reflects their important role in the processes of perception, concentration of attention and consolidation of memory, both on the cellular and at the system level. Connexins of glial cells are ubiquitously expressed in the brain, and the GJs formed by them provide molecular signaling and metabolic cooperation and play a certain role in the processes of neuronal migration during brain development, myelination, tissue homeostasis, and apoptosis. At the same time, mutations in the genes of glial connexins, as well as a deficiency of these proteins, are associated with such diseases as congenital neuropathies, hearing loss, skin diseases, and brain tumors. This review summarizes the existing data of numerous molecular, electrophysiological, pharmacological, and morphological studies aimed at progress in the study of the physiological and pathophysiological significance of glial and neuronal connexins and GJs for the central nervous system.

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31

Kapsner, Andreas. "Strong Connexivity". Thought: A Journal of Philosophy 1, n.º 2 (2012): 141–45. http://dx.doi.org/10.1002/tht.19.

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Connexive logics aim to capture important logical intuitions, intuitions that can be traced back to antiquity. However, the requirements that are imposed on connexive logic are actually not enough to do justice to these intuitions, as I will argue. I will suggest how these demands should be strengthened.

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32

Stauffer, K. A., N. M. Kumar, N. B. Gilula y N. Unwin. "Isolation and purification of gap junction channels." Journal of Cell Biology 115, n.º 1 (1 de octubre de 1991): 141–50. http://dx.doi.org/10.1083/jcb.115.1.141.

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This paper reports methods we have developed to solubilize gap junction channels, or connexons, from isolated gap junctions and to purify them in milligram quantities. Two sources of material are used: rat liver gap junctions and gap junctions produced by infecting insect cells with a baculovirus containing the cDNA for human liver beta 1 protein (connexin 32). Complete solubilization is obtained with long chain detergents (lauryl dimethyl amineoxide, dodecyl maltoside) and requires high ionic strength and high pH as well as reducing conditions. The purification involves chromatography on hydroxylapatite and gel filtration on Superose 6. A homogeneous product is indicated by a single band on a silver-stained gel and a homogeneous population of doughnut-shaped particles under the electron microscope. These particles have hexameric symmetry. The purified connexons have a tendency to form aggregates: filaments and sheets. The filaments grow by end-to-end association of connexons and are nonpolar, suggesting that the connexons are paired as in the cell-to-cell channel. The sheets grow by lateral association of the filaments.

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33

Goodenough, Daniel A., Jeffrey A. Goliger y David L. Paul. "Connexins, Connexons, and Intercellular Communication". Annual Review of Biochemistry 65, n.º 1 (junio de 1996): 475–502. http://dx.doi.org/10.1146/annurev.bi.65.070196.002355.

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34

Zhang, J. T., M. Chen, C. I. Foote y B. J. Nicholson. "Membrane integration of in vitro-translated gap junctional proteins: co- and post-translational mechanisms." Molecular Biology of the Cell 7, n.º 3 (marzo de 1996): 471–82. http://dx.doi.org/10.1091/mbc.7.3.471.

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Connexins (Cx) are protein components of gap junction channels that permit the passage of small molecules between neighboring cells. cDNAs of a large family of connexins have been isolated and sequenced. A gap junction channel consists of two connexons, one from each cell in contact, composed of six connexin subunits. It has been suggested by Musil and coworkers that the oligomerization of formation of a connexon occurs at the level of the trans-Golgi network. In the present study, we initiated an analysis of the early stages of protein synthesis and membrane insertion of Cx32 and Cx26, two connexins that we have demonstrated are co-expressed in the same junctions in hepatocytes. Using an in vitro transcription and a coupled cell-free translation and translocation system, we observed that both Cx32 and Cx26 could insert into microsome membranes co-translationally, producing a topological structure indistinguishable from that in isolated gap junctions. To our surprise, Cx26 could also insert into membranes post-translationally with a native orientation. This post-translational membrane insertion process is dependent on nucleotides but not their hydrolysis. Cx32, on the other hand, could not insert into membranes post-translationally. These disparate properties of Cx32 and Cx26 are not due to the significant difference in the lengths of their C-terminal domains, but rather to their internal amino acid sequences. These observations raise the possibility that there may be another pathway for Cx26 to insert into membranes in cells and this feature may be important for the regulation of its functions. These findings may also lead us to a new approach to reconstitution without detergent extraction.

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35

Unger, V. M., D. W. Entrikin, X. Guan, N. M. Kumar, N. B. Gilula y M. Yeager. "Structure of a Recombinant Gap Junction Channel at 7Å Resolution". Microscopy and Microanalysis 4, S2 (julio de 1998): 464–65. http://dx.doi.org/10.1017/s1431927600022443.

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Gap junction membrane channels mediate the electrical and metabolic coupling between cells. The channels are formed by the end-to-end docking of two hemichannels (connexons), each of which is formed by a hexameric cluster of protein subunits (connexins). The principal gap junction protein in the heart, α1 connexin (also designated Cx43), mediates action potential propagation between cells in order to synchronize cardiac contraction.We recently utilized electron cryo-microscopy and image analysis to examine frozen-hydrated two-dimensional (2D) crystals of a recombinant, truncated α1- connexin (α1Cx263T). The projection map at 7Å resolution revealed that each 30kD connexin subunit has a transmembrane α-helix that lines the aqueous pore and a second α-helix in close contact with the membrane lipids [Nature Struct. Biol. 4: 39-43 (1997)]. The distribution of densities allowed us to propose a model in which the two apposing connexons that form the channel are staggered by ∼30°. Furthermore, apparent non-crystallographic twofold axes predicted that the two apposing connexons adopt identical conformations.

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36

Debarre, Olivier. "Theoremes de Connexite et Varietes Abeliennes". American Journal of Mathematics 117, n.º 3 (junio de 1995): 787. http://dx.doi.org/10.2307/2375089.

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37

Wansing, Heinrich y Hitoshi Omori. "A Note on “A Connexive Conditional”". Logos & Episteme 13, n.º 3 (2022): 325–28. http://dx.doi.org/10.5840/logos-episteme202213326.

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38

Drewes, Lester R. "Making Connexons in the Neurovascular Unit". Journal of Cerebral Blood Flow & Metabolism 32, n.º 8 (4 de abril de 2012): 1455–56. http://dx.doi.org/10.1038/jcbfm.2012.44.

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39

Baumeister, W. y R. Hegerl. "Can S-layers make bacterial connexons?" FEMS Microbiology Letters 36, n.º 2-3 (septiembre de 1986): 119–25. http://dx.doi.org/10.1111/j.1574-6968.1986.tb01680.x.

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40

LIANG, YONGQI. "Approximation faible pour les 0-cycles sur un produit de variétés rationnellement connexes". Mathematical Proceedings of the Cambridge Philosophical Society 164, n.º 3 (20 de marzo de 2017): 485–91. http://dx.doi.org/10.1017/s0305004117000330.

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RésuméConsidérons l'approximation faible de 0-cycles sur une variété propre lisse définie sur un corps de nombres, elle est conjecturée d'étre contrôlée par le groupe de Brauer de la variété. Soit X une surface de Châtelet ou une compactification lisse d'un espace homogéne d'un groupe algébrique linéaire connexe à stabilisateur connexe. Soit Y une variété rationnellement connexe. Nous montrons que l'approximation faible de 0-cycles sur le produit X × Y est contrôlée par son groupe de Brauer si c'est le cas pour Y après toute extension finie du corps de base. Nous ne supposons l'existence de 0-cycles de degré 1 ni sur X ni sur Y.

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41

Jarmużek, Tomasz y Jacek Malinowski. "Modal Boolean Connexive Logics: Semantics and Tableau Approach". Bulletin of the Section of Logic 48, n.º 3 (30 de octubre de 2019): 213–43. http://dx.doi.org/10.18778/0138-0680.48.3.05.

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In this paper we investigate Boolean connexive logics in a language with modal operators: □, ◊. In such logics, negation, conjunction, and disjunction behave in a classical, Boolean way. Only implication is non-classical. We construct these logics by mixing relating semantics with possible worlds. This way, we obtain connexive counterparts of basic normal modal logics. However, most of their traditional axioms formulated in terms of modalities and implication do not hold anymore without additional constraints, since our implication is weaker than the material one. In the final section, we present a tableau approach to the discussed modal logics.

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42

Rico, Felix, Atsunori Oshima, Yoshinori Fujiyoshi, Peter Hinterdorfer y Simon Scheuring. "Binding Kinetics of Inter-Connexon Interaction". Biophysical Journal 100, n.º 3 (febrero de 2011): 564a. http://dx.doi.org/10.1016/j.bpj.2010.12.3273.

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43

Li, Xinbo. "Seeing Is Believing: Gap Junctions in Motion". Biology 10, n.º 6 (2 de junio de 2021): 494. http://dx.doi.org/10.3390/biology10060494.

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44

Comité de rédaction, Le. "Création de la revue Connexe". Connexe : les espaces postcommunistes en question(s) 1 (12 de julio de 2015): 7–9. http://dx.doi.org/10.5077/journals/connexe.2015.e30.

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Transitions, la revue publiée depuis 1993 par l’Université libre de Bruxelles et depuis 2000 en partenariat avec l’Université de Genève, n’est plus. Fin de Transitions, place à Connexe : les espaces postcommunistes en question(s). Ce titre désigne à lui seul l’ampleur de nos ambitions : mettre en relation des disciplines et objets de recherche voisins, tisser des liens entre des domaines et des espaces « connexes », saisir à la fois le multiple et le commun, la singularité et l’ensemble, le présent et le passé, le régional et le transnational, la revue s’intéressant à un large espace géographique, qui intègre les anciennes « démocraties populaires » et les anciennes Républiques de l’Union soviétique.

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45

Wansing, Heinrich y Daniel Skurt. "Negation as Cancellation, Connexive Logic, and qLPm". Australasian Journal of Logic 15, n.º 2 (5 de julio de 2018): 476. http://dx.doi.org/10.26686/ajl.v15i2.4869.

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In this paper, we shall consider the so-called cancellation view of negation and the inferential role of contradictions. We will discuss some of the problematic aspects of negation as cancellation, such as its original presentation by Richard and Valery Routley and its role in motivating connexive logic. Furthermore, we will show that the idea of inferential ineffectiveness of contradictions can be conceptually separated from the cancellation model of negation by developing a system we call qLPm, a combination of Graham Priest’s minimally inconsistent Logic of Paradox with q-entailment (quasi-entailment) as introduced by Grzegorz Malinowski.

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46

Jiang, J. X. y D. A. Goodenough. "Heteromeric connexons in lens gap junction channels." Proceedings of the National Academy of Sciences 93, n.º 3 (6 de febrero de 1996): 1287–91. http://dx.doi.org/10.1073/pnas.93.3.1287.

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47

Prochnow, Nora y Rolf Dermietzel. "Connexons and cell adhesion: a romantic phase". Histochemistry and Cell Biology 130, n.º 1 (15 de mayo de 2008): 71–77. http://dx.doi.org/10.1007/s00418-008-0434-7.

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48

Wright, Josephine A., Toby Richards y David L. Becker. "Connexins and Diabetes". Cardiology Research and Practice 2012 (2012): 1–8. http://dx.doi.org/10.1155/2012/496904.

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Cell-to-cell interactions via gap junctional communication and connexon hemichannels are involved in the pathogenesis of diabetes. Gap junctions are highly specialized transmembrane structures that are formed by connexon hemichannels, which are further assembled from proteins called “connexins.” In this paper, we discuss current knowledge about connexins in diabetes. We also discuss mechanisms of connexin influence and the role of individual connexins in various tissues and how these are affected in diabetes. Connexins may be a future target by both genetic and pharmacological approaches to develop treatments for the treatment of diabetes and its complications.

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49

Thévenin, Anastasia F., Tia J. Kowal, John T. Fong, Rachael M. Kells, Charles G. Fisher y Matthias M. Falk. "Proteins and Mechanisms Regulating Gap-Junction Assembly, Internalization, and Degradation". Physiology 28, n.º 2 (marzo de 2013): 93–116. http://dx.doi.org/10.1152/physiol.00038.2012.

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Gap junctions (GJs) are the only known cellular structures that allow a direct cell-to-cell transfer of signaling molecules by forming densely packed arrays or “plaques” of hydrophilic channels that bridge the apposing membranes of neighboring cells. The crucial role of GJ-mediated intercellular communication (GJIC) for all aspects of multicellular life, including coordination of development, tissue function, and cell homeostasis, has been well documented. Assembly and degradation of these membrane channels is a complex process that includes biosynthesis of the connexin (Cx) subunit proteins (innexins in invertebrates) on endoplasmic reticulum (ER) membranes, oligomerization of compatible subunits into hexameric hemichannels (connexons), delivery of the connexons to the plasma membrane (PM), head-on docking of compatible connexons in the extracellular space at distinct locations, arrangement of channels into dynamic spatially and temporally organized GJ channel plaques, as well as internalization of GJs into the cytoplasm followed by their degradation. Clearly, precise modulation of GJIC, biosynthesis, and degradation are crucial for accurate function, and much research currently addresses how these fundamental processes are regulated. Here, we review posttranslational protein modifications (e.g., phosphorylation and ubiquitination) and the binding of protein partners (e.g., the scaffolding protein ZO-1) known to regulate GJ biosynthesis, internalization, and degradation. We also look closely at the atomic resolution structure of a GJ channel, since the structure harbors vital cues relevant to GJ biosynthesis and turnover.

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50

SÁEZ, JUAN C., VIVIANA M. BERTHOUD, MARÍA C. BRAÑES, AGUSTÍN D. MARTÍNEZ y ERIC C. BEYER. "Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions". Physiological Reviews 83, n.º 4 (octubre de 2003): 1359–400. http://dx.doi.org/10.1152/physrev.00007.2003.

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Sáez, Juan C., Viviana M. Berthoud, María C. Brañes, Agustín D. Martínez, and Eric C. Beyer. Plasma Membrane Channels Formed by Connexins: Their Regulation and Functions. Physiol Rev 83: 1359-1400, 2003; 10.1152/physrev.00007.2003.—Members of the connexin gene family are integral membrane proteins that form hexamers called connexons. Most cells express two or more connexins. Open connexons found at the nonjunctional plasma membrane connect the cell interior with the extracellular milieu. They have been implicated in physiological functions including paracrine intercellular signaling and in induction of cell death under pathological conditions. Gap junction channels are formed by docking of two connexons and are found at cell-cell appositions. Gap junction channels are responsible for direct intercellular transfer of ions and small molecules including propagation of inositol trisphosphate-dependent calcium waves. They are involved in coordinating the electrical and metabolic responses of heterogeneous cells. New approaches have expanded our knowledge of channel structure and connexin biochemistry (e.g., protein trafficking/assembly, phosphorylation, and interactions with other connexins or other proteins). The physiological role of gap junctions in several tissues has been elucidated by the discovery of mutant connexins associated with genetic diseases and by the generation of mice with targeted ablation of specific connexin genes. The observed phenotypes range from specific tissue dysfunction to embryonic lethality.

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