The Experts below are selected from a list of 93 Experts worldwide ranked by ideXlab platform
Marc Thiry - One of the best experts on this subject based on the ideXlab platform.
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Tricellular adherens Junctions provide a cell surface delivery platform for connexin 26 30 oligomers in the cochlea
Hearing Research, 2021Co-Authors: Jean Defourny, Marc ThiryAbstract:In the cochlea, connexins 26 (Cx26) and 30 (Cx30) largely co-assemble into heteromeric gap Junctions, which connect adjacent non-sensory epithelial cells. These channels are believed to ensure the rapid removal of K+ away from the base of sensory hair cells, resulting in K+ recycling back to the endolymph to maintain cochlear homeostasis. Many of the mutations in GJB2 and GJB6, which encode CX26 and CX30, impair the formation of membrane channels and cause autosomal hearing loss in humans. Although recent advances have been made, several important questions remain about connexin trafficking and gap Junction biogenesis. Here we show that Tricellular adherens Junctions present at the crossroad between adjacent gap Junction plaques, provide an unexpected cell surface delivery platform for Cx26/Cx30 oligomers. Using an in situ proximity ligation assay, we detected the presence of non-Junctional Cx26/Cx30 oligomers within lipid raft-enriched Tricellular Junction sites. In addition, we observed that cadherin homophilic interactions are critically involved in microtubule-mediated trafficking of Cx26/Cx30 oligomers to the cell surface. Overall, our results unveil an unexpected role for Tricellular Junctions in the trafficking and assembly of membrane channels.
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Tricellular adherens Junctions provide a cell surface delivery platform for connexin 26 30 oligomers in the cochlea
Social Science Research Network, 2020Co-Authors: Jean Defourny, Marc ThiryAbstract:Many of the mutations in GJB2 and GJB6, which encode connexins 26 and 30 (CX26 and CX30), impair the formation of membrane channels and cause autosomal hearing loss in humans. In the cochlea, Cx26 and Cx30 largely co-assemble into heteromeric channels, which connect adjacent non-sensory epithelial cells. Although recent advances have been made, several important questions remain about connexin trafficking and gap Junction biogenesis. Here we show that Tricellular adherens Junctions present at the crossroad between adjacent gap Junction plaques, provide an unexpected cell surface delivery platform for Cx26/Cx30 oligomers. Using an in situ proximity ligation assay, we detected the presence of non-Junctional Cx26/Cx30 oligomers within lipid raft-enriched Tricellular Junction sites. In addition, we observed that cadherin homophilic interactions are critically involved in microtubule-mediated trafficking of Cx26/Cx30 oligomers to the cell surface. Overall, our results unveil an unexpected role for Tricellular Junctions in the trafficking and assembly of membrane channels.
Vanessa J Auld - One of the best experts on this subject based on the ideXlab platform.
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scribble and discs large mediate Tricellular Junction formation
Development, 2019Co-Authors: Zohreh Sharifkhodaei, Mary M Gilbert, Vanessa J AuldAbstract:ABSTRACT Junctional complexes that mediate cell adhesion are key to epithelial integrity, cell division and permeability barrier formation. In Drosophila, the scaffolding proteins Scribble (Scrib) and Discs Large (Dlg) are key regulators of epithelial polarity, proliferation, assembly of Junctions and protein trafficking. We found that Scrib and Dlg are necessary for the formation of the Tricellular Junction (TCJ), a unique Junction that forms in epithelia at the point of convergence of three neighboring cells. Scrib and Dlg are in close proximity with the TCJ proteins Gliotactin (Gli) and Bark Beetle (Bark), and both are required for TCJ protein recruitment. Loss of Bark or Gli led to basolateral spread of the TCJ complex at the cell corners. Loss of the septate Junction proteins Nrx-IV and the Na+/K+ ATPase also resulted in basolateral spread of the entire TCJ complex at the cell corners. The Scrib PDZ1-2 domains and the Dlg GUK domain are necessary for Bark and Gli localization to the TCJ. Overall, we propose a model in which Scrib and Dlg are key components of the TCJ, and form a complex with Bark and Gli.
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c terminal src kinase csk regulates the Tricellular Junction protein gliotactin independent of src
Molecular Biology of the Cell, 2018Co-Authors: Gayathri Samarasekera, Vanessa J AuldAbstract:Tricellular Junctions (TCJs) are uniquely placed permeability barriers formed at the corners of polarized epithelia where tight Junctions in vertebrates or septate Junctions (SJ) in invertebrates from three cells converge. Gliotactin is a Drosophila TCJ protein, and loss of Gliotactin results in SJ and TCJ breakdown and permeability barrier loss. When overexpressed, Gliotactin spreads away from the TCJs, resulting in disrupted epithelial architecture, including overproliferation, cell delamination, and migration. Gliotactin levels are tightly controlled at the mRNA level and at the protein level through endocytosis and degradation triggered by tyrosine phosphorylation. We identified C-terminal Src kinase (Csk) as a tyrosine kinase responsible for regulating Gliotactin endocytosis. Increased Csk suppresses the Gliotactin overexpression phenotypes by increasing endocytosis. Loss of Csk causes Gliotactin to spread away from the TCJ. Although Csk is known as a negative regulator of Src kinases, the effects of Csk on Gliotactin are independent of Src and likely occur through an adherens Junction associated complex. Overall, we identified a new Src-independent role for Csk in the control of Gliotactin, a key Tricellular Junction protein.
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gliotactin and discs large form a protein complex at the Tricellular Junction of polarized epithelial cells in drosophila
Journal of Cell Science, 2006Co-Authors: Joost Schulte, Kristi Charish, Jaimmie Que, Sarah Ravn, Christina Mackinnon, Vanessa J AuldAbstract:The Tricellular Junction (TCJ) forms at the convergence of pleated septate Junctions (SJs) from three adjacent cells in polarized epithelia and is necessary for maintaining the transepithelial barrier. In Drosophila, the transmembrane protein Gliotactin was the first identified marker of the TCJ, but little is known about other molecular constituents. We now show that Gliotactin associates with Discs large at the TCJ in a Ca(2+)-dependent manner. Discs large is essential for the formation of the TCJ and the localization of Gliotactin. Surprisingly, Gliotactin localization at the TCJ was independent of its PDZ-binding motif and Gliotactin did not bind directly to Discs large. Therefore Gliotactin and Discs large association is through intermediary proteins at the TCJ. Gliotactin can associate with other septate Junction proteins but this was detected only when Gliotactin was overexpressed and spread throughout the septate Junction domain. Gliotactin overexpression and spread also resulted in a reduction of Discs large staining but not vice versa. These results suggest that Discs large participates in different protein interactions in the SJ and the TCJ. Finally this work supports a model where Gliotactin and Dlg are components of a larger protein complex that links the converging SJs with the TCJ to create the transepithelial barrier.
Jean Defourny - One of the best experts on this subject based on the ideXlab platform.
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Tricellular adherens Junctions provide a cell surface delivery platform for connexin 26 30 oligomers in the cochlea
Hearing Research, 2021Co-Authors: Jean Defourny, Marc ThiryAbstract:In the cochlea, connexins 26 (Cx26) and 30 (Cx30) largely co-assemble into heteromeric gap Junctions, which connect adjacent non-sensory epithelial cells. These channels are believed to ensure the rapid removal of K+ away from the base of sensory hair cells, resulting in K+ recycling back to the endolymph to maintain cochlear homeostasis. Many of the mutations in GJB2 and GJB6, which encode CX26 and CX30, impair the formation of membrane channels and cause autosomal hearing loss in humans. Although recent advances have been made, several important questions remain about connexin trafficking and gap Junction biogenesis. Here we show that Tricellular adherens Junctions present at the crossroad between adjacent gap Junction plaques, provide an unexpected cell surface delivery platform for Cx26/Cx30 oligomers. Using an in situ proximity ligation assay, we detected the presence of non-Junctional Cx26/Cx30 oligomers within lipid raft-enriched Tricellular Junction sites. In addition, we observed that cadherin homophilic interactions are critically involved in microtubule-mediated trafficking of Cx26/Cx30 oligomers to the cell surface. Overall, our results unveil an unexpected role for Tricellular Junctions in the trafficking and assembly of membrane channels.
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Tricellular adherens Junctions provide a cell surface delivery platform for connexin 26 30 oligomers in the cochlea
Social Science Research Network, 2020Co-Authors: Jean Defourny, Marc ThiryAbstract:Many of the mutations in GJB2 and GJB6, which encode connexins 26 and 30 (CX26 and CX30), impair the formation of membrane channels and cause autosomal hearing loss in humans. In the cochlea, Cx26 and Cx30 largely co-assemble into heteromeric channels, which connect adjacent non-sensory epithelial cells. Although recent advances have been made, several important questions remain about connexin trafficking and gap Junction biogenesis. Here we show that Tricellular adherens Junctions present at the crossroad between adjacent gap Junction plaques, provide an unexpected cell surface delivery platform for Cx26/Cx30 oligomers. Using an in situ proximity ligation assay, we detected the presence of non-Junctional Cx26/Cx30 oligomers within lipid raft-enriched Tricellular Junction sites. In addition, we observed that cadherin homophilic interactions are critically involved in microtubule-mediated trafficking of Cx26/Cx30 oligomers to the cell surface. Overall, our results unveil an unexpected role for Tricellular Junctions in the trafficking and assembly of membrane channels.
Yohanns Bellaïche - One of the best experts on this subject based on the ideXlab platform.
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Tricellular Junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis
Journal of Cell Science, 2018Co-Authors: Zhimin Wang, Floris Bosveld, Yohanns BellaïcheAbstract:In epithelial tissue, new cell-cell Junctions are formed upon cytokinesis. To understand Junction formation during cytokinesis, we explored de novo formation of Tricellular septate Junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens Junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate Junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis.
Zhimin Wang - One of the best experts on this subject based on the ideXlab platform.
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Tricellular Junction proteins promote disentanglement of daughter and neighbour cells during epithelial cytokinesis
Journal of Cell Science, 2018Co-Authors: Zhimin Wang, Floris Bosveld, Yohanns BellaïcheAbstract:In epithelial tissue, new cell-cell Junctions are formed upon cytokinesis. To understand Junction formation during cytokinesis, we explored de novo formation of Tricellular septate Junctions (TCJs) in Drosophila epithelium. We found that upon midbody formation, the membranes of the two daughter cells and of the neighbouring cells located below the adherens Junction (AJ) remain entangled in a 4-cell structure apposed to the midbody. The septate Junction protein Discs-Large and components of the TCJ, Gliotactin and Anakonda accumulate in this 4-cell structure. Subsequently, a basal movement of the midbody parallels the detachment of the neighbouring cell membranes from the midbody, the disengagement of the daughter cells from their neighbours and the reorganisation of TCJs between the two daughter cells and their neighbouring cells. While the movement of midbody is independent of the Alix and Shrub abscission regulators, the loss of Gliotactin or Anakonda function impedes both the resolution of the connection between the daughter-neighbour cells and midbody movement. TCJ proteins therefore control an additional step of cytokinesis necessary for the disentanglement of the daughter cells from their neighbours during cytokinesis.
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studying the formation of Tricellular Junction upon epithelial cell division in drosophila
2017Co-Authors: Zhimin WangAbstract:Pour maintenir l'organisation et la polarite du tissu epithelial, de nouvelles jonctions cellulaires ont besoin de se former lors de la division cellulaire. Pour comprendre les mecanismes de formation de la jonction durant la cytokinese, nous avons explore dans les tissus epitheliaux de la Drosophile, la formation des jonctions septees tricellulaires (TCJs), critique a la fois dans la fonction de barriere tissulaire, dans l'homeostasie des cellules souches, ainsi que dans l'orientation du fuseau mitotique. Durant les dernieres etapes de la constriction de l'anneau contractile, les membranes des deux cellules filles et des cellules voisines localisees sous la jonction adherente (JA) restent enchevetrees dans une structure a 4 cellules apposee au corps intermediaire. Les constituants proteiques de la jonction septee, Discs-large (Dlg) et Neuroglian (Nrg), ainsi que les composants de la TCJ, Gliotactin (Gli) et Anakonda (Aka), s'accumulent dans cette structure a 4 cellules. Par la suite, la descente basale du corps intermediaire est correlee au detachement des membranes des cellules voisines, au desengagement des cellules filles de leurs voisines, et a la formation de TCJs matures. Le detachement des cellules voisines du corps intermediaire est independant de l'abscision. Au contraire, la perte de la fonction Gli ou Aka empeche le detachement entre les cellules filles-voisines et le mouvement du corps intermediaire. Ainsi, nous proposons que les proteines de la TCJ controlent une etape additionnelle de la cytokinese, necessaire au desengagement des cellules filles et de leurs voisines durant la cytokinese epitheliale.
