The Experts below are selected from a list of 210 Experts worldwide ranked by ideXlab platform
Greg J. Beitel - One of the best experts on this subject based on the ideXlab platform.
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Cell Junctions: lessons from a broken heart.
Current biology : CB, 2009Co-Authors: Kevin S. Nelson, Greg J. BeitelAbstract:In a case of the familiar being strange, new work shows that the integrity of the Drosophila cardiac system depends on Septate-junction proteins even though the heart lacks discernable Septate Junctions.
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Sinuous is a Drosophila claudin required for Septate junction organization and epithelial tube size control.
The Journal of cell biology, 2004Co-Authors: Joost Schulte, Alexander Hirschi, Ulrich Tepass, Greg J. BeitelAbstract:Epithelial tubes of the correct size and shape are vital for the function of the lungs, kidneys, and vascular system, yet little is known about epithelial tube size regulation. Mutations in the Drosophila gene sinuous have previously been shown to cause tracheal tubes to be elongated and have diameter increases. Our genetic analysis using a sinuous null mutation suggests that sinuous functions in the same pathway as the Septate junction genes neurexin and scribble, but that nervana 2, convoluted, varicose, and cystic have functions not shared by sinuous. Our molecular analyses reveal that sinuous encodes a claudin that localizes to Septate Junctions and is required for Septate junction organization and paracellular barrier function. These results provide important evidence that the paracellular barriers formed by arthropod Septate Junctions and vertebrate tight Junctions have a common molecular basis despite their otherwise different molecular compositions, morphologies, and subcellular localizations.
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A junctional problem of apical proportions: epithelial tube-size control by Septate Junctions in the Drosophila tracheal system
Current opinion in cell biology, 2004Co-Authors: Greg J. BeitelAbstract:The size of epithelial tubes is critical for the function of organs such as the lung, kidney and vascular system. However, the molecular mechanisms regulating tube size are largely unknown. Recent work in the Drosophila tracheal system reveals that Septate Junctions play a previously unsuspected role in tube-size control. Surprisingly, this tube-size function is distinct from the established diffusion barrier function of Septate Junctions, and involves regulation of cell shape rather than cell number. Possible tube-size functions of Septate Junctions include patterning of the apical extracellular matrix and regulation of conserved cell polarity genes such as Scribble and Discs Large.
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The Na+/K+ ATPase is required for Septate junction function and epithelial tube-size control in the Drosophila tracheal system.
Development (Cambridge England), 2003Co-Authors: Sarah M. Paul, Melissa Ternet, Paul M. Salvaterra, Greg J. BeitelAbstract:Although the correct architecture of epithelial tubes is crucial for the function of organs such as the lung, kidney and vascular system, little is known about the molecular mechanisms that control tube size. We show that mutations in the ATPalpha alpha and nrv2 beta subunits of the Na+/K+ ATPase cause Drosophila tracheal tubes to have increased lengths and expanded diameters. ATPalpha and nrv2 mutations also disrupt stable formation of Septate Junctions, structures with some functional and molecular similarities to vertebrate tight Junctions. The Nrv2 beta subunit isoforms have unique tube size and junctional functions because Nrv2, but not other Drosophila Na+/K+ ATPase beta subunits, can rescue nrv2 mutant phenotypes. Mutations in known Septate Junctions genes cause the same tracheal tube-size defects as ATPalpha and nrv2 mutations, indicating that Septate Junctions have a previously unidentified role in epithelial tube-size control. Double mutant analyses suggest that tube-size control by Septate Junctions is mediated by at least two discernable pathways, although the paracellular diffusion barrier function does not appear to involved because tube-size control and diffusion barrier function are genetically separable. Together, our results demonstrate that specific isoforms of the Na+/K+ ATPase play a crucial role in Septate junction function and that Septate Junctions have multiple distinct functions that regulate paracellular transport and epithelial tube size.
Mikio Furuse - One of the best experts on this subject based on the ideXlab platform.
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The Septate junction protein Mesh is required for epithelial morphogenesis, ion transport, and paracellular permeability in the Drosophila Malpighian tubule.
American journal of physiology. Cell physiology, 2020Co-Authors: Sima Jonusaite, Mikio Furuse, Yasushi Izumi, Klaus W. Beyenbach, Heiko Meyer, Achim Paululat, Aylin R. RodanAbstract:Septate Junctions (SJs) are occluding cell-cell Junctions that have roles in paracellular permeability and barrier function in the epithelia of invertebrates. Arthropods have two types of SJs, plea...
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Septate Junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila.
Journal of cell science, 2019Co-Authors: Yasushi Izumi, Kyoko Furuse, Mikio FuruseAbstract:Smooth Septate Junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in the Drosophila midgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in the Drosophila adult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ-protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, reduced the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut.
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Septate Junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila
2019Co-Authors: Yasushi Izumi, Kyoko Furuse, Mikio FuruseAbstract:Abstract Smooth Septate Junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in the Drosophila midgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in the Drosophila adult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, suppressed the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut. Summary statement Depletion of smooth Septate junction-associated proteins from enterocytes in the Drosophila adult midgut results in intestinal hypertrophy accompanied by accumulation of morphologically aberrant enterocytes and increased stem cell proliferation.
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Molecular dissection of smooth Septate Junctions: understanding their roles in arthropod physiology.
Annals of the New York Academy of Sciences, 2017Co-Authors: Mikio Furuse, Yasushi IzumiAbstract:Smooth Septate Junctions (sSJs) are cell-cell Junctions that are thought to regulate the paracellular pathway of the intestine and renal system in arthropods. The detailed mechanism of action of sSJs is not well understood, because their molecular organization has remained elusive for a long time. Recently, two sSJ-specific membrane proteins, Ssk and Mesh, were identified by screening monoclonal antibodies raised against sSJ-containing membrane fractions isolated from the silkworm midgut. Furthermore, a genetic screen in Drosophila based on microscopic observation of sSJ formation identified Tsp2A as a novel sSJ-specific membrane protein. Together with Tsp2A, Ssk and Mesh form a protein complex, and all three proteins are required for sSJ formation, as well as intestinal barrier function in Drosophila. Additional studies are likely to elucidate their roles in (1) the formation and reorganization of sSJs, (2) paracellular barrier functions and permselectivity, and (3) short-term and long-term regulation of paracellular functions in arthropod epithelia.
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A tetraspanin regulates Septate junction formation in Drosophila midgut.
Journal of cell science, 2016Co-Authors: Yasushi Izumi, Kyoko Furuse, Minako Motoishi, Mikio FuruseAbstract:Septate Junctions (SJs) are membrane specializations that restrict the free diffusion of solutes through the paracellular pathway in invertebrate epithelia. In arthropods, two morphologically different types of Septate Junctions are observed; pleated (pSJs) and smooth (sSJs), which are present in ectodermally and endodermally derived epithelia, respectively. Recent identification of sSJ-specific proteins, Mesh and Ssk, in Drosophila indicates that the molecular compositions of sSJs and pSJs differ. A deficiency screen based on immunolocalization of Mesh identified a tetraspanin family protein, Tsp2A, as a newly discovered protein involved in sSJ formation in Drosophila Tsp2A specifically localizes at sSJs in the midgut and Malpighian tubules. Compromised Tsp2A expression caused by RNAi or the CRISPR/Cas9 system was associated with defects in the ultrastructure of sSJs, changed localization of other sSJ proteins, and impaired barrier function of the midgut. In most Tsp2A mutant cells, Mesh failed to localize to sSJs and was distributed through the cytoplasm. Tsp2A forms a complex with Mesh and Ssk and these proteins are mutually interdependent for their localization. These observations suggest that Tsp2A cooperates with Mesh and Ssk to organize sSJs.
Yasushi Izumi - One of the best experts on this subject based on the ideXlab platform.
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The Septate junction protein Mesh is required for epithelial morphogenesis, ion transport, and paracellular permeability in the Drosophila Malpighian tubule.
American journal of physiology. Cell physiology, 2020Co-Authors: Sima Jonusaite, Mikio Furuse, Yasushi Izumi, Klaus W. Beyenbach, Heiko Meyer, Achim Paululat, Aylin R. RodanAbstract:Septate Junctions (SJs) are occluding cell-cell Junctions that have roles in paracellular permeability and barrier function in the epithelia of invertebrates. Arthropods have two types of SJs, plea...
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Septate Junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila.
Journal of cell science, 2019Co-Authors: Yasushi Izumi, Kyoko Furuse, Mikio FuruseAbstract:Smooth Septate Junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in the Drosophila midgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in the Drosophila adult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ-protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, reduced the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut.
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Septate Junctions regulate gut homeostasis through regulation of stem cell proliferation and enterocyte behavior in Drosophila
2019Co-Authors: Yasushi Izumi, Kyoko Furuse, Mikio FuruseAbstract:Abstract Smooth Septate Junctions (sSJs) contribute to the epithelial barrier, which restricts leakage of solutes through the paracellular route of epithelial cells in the Drosophila midgut. We previously identified three sSJ-associated membrane proteins, Ssk, Mesh, and Tsp2A, and showed that these proteins were required for sSJ formation and intestinal barrier function in the larval midgut. Here, we investigated the roles of sSJs in the Drosophila adult midgut. Depletion of any of the sSJ-proteins from enterocytes resulted in remarkably shortened lifespan and intestinal barrier dysfunction in flies. Interestingly, the sSJ protein-deficient flies showed intestinal hypertrophy accompanied by accumulation of morphologically abnormal enterocytes. The phenotype was associated with increased stem cell proliferation and activation of the MAP kinase and Jak-Stat pathways in stem cells. Loss of cytokines Unpaired2 and Unpaired3, which are involved in Jak-Stat pathway activation, suppressed the intestinal hypertrophy, but not the increased stem cell proliferation, in flies lacking Mesh. The present findings suggest that SJs play a crucial role in maintaining tissue homeostasis through regulation of stem cell proliferation and enterocyte behavior in the Drosophila adult midgut. Summary statement Depletion of smooth Septate junction-associated proteins from enterocytes in the Drosophila adult midgut results in intestinal hypertrophy accompanied by accumulation of morphologically aberrant enterocytes and increased stem cell proliferation.
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Molecular dissection of smooth Septate Junctions: understanding their roles in arthropod physiology.
Annals of the New York Academy of Sciences, 2017Co-Authors: Mikio Furuse, Yasushi IzumiAbstract:Smooth Septate Junctions (sSJs) are cell-cell Junctions that are thought to regulate the paracellular pathway of the intestine and renal system in arthropods. The detailed mechanism of action of sSJs is not well understood, because their molecular organization has remained elusive for a long time. Recently, two sSJ-specific membrane proteins, Ssk and Mesh, were identified by screening monoclonal antibodies raised against sSJ-containing membrane fractions isolated from the silkworm midgut. Furthermore, a genetic screen in Drosophila based on microscopic observation of sSJ formation identified Tsp2A as a novel sSJ-specific membrane protein. Together with Tsp2A, Ssk and Mesh form a protein complex, and all three proteins are required for sSJ formation, as well as intestinal barrier function in Drosophila. Additional studies are likely to elucidate their roles in (1) the formation and reorganization of sSJs, (2) paracellular barrier functions and permselectivity, and (3) short-term and long-term regulation of paracellular functions in arthropod epithelia.
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A tetraspanin regulates Septate junction formation in Drosophila midgut.
Journal of cell science, 2016Co-Authors: Yasushi Izumi, Kyoko Furuse, Minako Motoishi, Mikio FuruseAbstract:Septate Junctions (SJs) are membrane specializations that restrict the free diffusion of solutes through the paracellular pathway in invertebrate epithelia. In arthropods, two morphologically different types of Septate Junctions are observed; pleated (pSJs) and smooth (sSJs), which are present in ectodermally and endodermally derived epithelia, respectively. Recent identification of sSJ-specific proteins, Mesh and Ssk, in Drosophila indicates that the molecular compositions of sSJs and pSJs differ. A deficiency screen based on immunolocalization of Mesh identified a tetraspanin family protein, Tsp2A, as a newly discovered protein involved in sSJ formation in Drosophila Tsp2A specifically localizes at sSJs in the midgut and Malpighian tubules. Compromised Tsp2A expression caused by RNAi or the CRISPR/Cas9 system was associated with defects in the ultrastructure of sSJs, changed localization of other sSJ proteins, and impaired barrier function of the midgut. In most Tsp2A mutant cells, Mesh failed to localize to sSJs and was distributed through the cytoplasm. Tsp2A forms a complex with Mesh and Ssk and these proteins are mutually interdependent for their localization. These observations suggest that Tsp2A cooperates with Mesh and Ssk to organize sSJs.
Manzoor A Bhat - One of the best experts on this subject based on the ideXlab platform.
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a laminin g egf laminin g module in neurexin iv is essential for the apico lateral localization of contactin and organization of Septate Junctions
PLOS ONE, 2011Co-Authors: Swati Banerjee, Alan S Fanning, Raehum Paik, Rosa E Mino, Kevin Blauth, Elizabeth S Fisher, Victoria J Madden, Manzoor A BhatAbstract:Septate Junctions (SJs) display a unique ultrastructural morphology with ladder-like electron densities that are conserved through evolution. Genetic and molecular analyses have identified a highly conserved core complex of SJ proteins consisting of three cell adhesion molecules Neurexin IV, Contactin, and Neuroglian, which interact with the cytoskeletal FERM domain protein Coracle. How these individual proteins interact to form the septal arrays that create the paracellular barrier is poorly understood. Here, we show that point mutations that map to specific domains of neurexin IV lead to formation of fewer septae and disorganization of SJs. Consistent with these observations, our in vivo domain deletion analyses identified the first Laminin G-EGF-Laminin G module in the extracellular region of Neurexin IV as necessary for the localization of and association with Contactin. Neurexin IV protein that is devoid of its cytoplasmic region is able to create septae, but fails to form a full complement of SJs. These data provide the first in vivo evidence that specific domains in Neurexin IV are required for protein-protein interactions and organization of SJs. Given the molecular conservation of SJ proteins across species, our studies may provide insights into how vertebrate axo-glial SJs are organized in myelinated axons.
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The Cytoskeletal Adaptor Protein Band 4.1B Is Required for the Maintenance of Paranodal Axoglial Septate Junctions in Myelinated Axons
The Journal of Neuroscience, 2011Co-Authors: Elizabeth D Buttermore, Jeffrey L Dupree, Jr-gang Cheng, Lino Tessarollo, Xiuli An, Manzoor A BhatAbstract:Precise targeting and maintenance of axonal domains in myelinated axons is essential for saltatory conduction. Caspr and Caspr2, which localize at paranodal and juxtaparanodal domains, contain binding sites for the cytoskeletal adaptor protein 4.1B. The exact role of 4.1B in the organization and maintenance of axonal domains is still not clear. Here, we report the generation and characterization of 4.1B -null mice. We show that loss of 4.1B in the PNS results in mislocalization of Caspr at paranodes and destabilization of paranodal axoglial Septate Junctions (AGSJs) as early as postnatal day 30. In the CNS, Caspr localization is progressively disrupted and ultrastructural analysis showed paranodal regions that were completely devoid of AGSJs, with axolemma separated from the myelin loops, and loops coming off the axolemma. Most importantly, our phenotypic analysis of previously generated 4.1B mutants, used in the study by [Horresh et al. (2010)][1], showed that Caspr localization was not affected in the PNS, even after 1 year; and 4.1R was neither expressed, nor enriched at the paranodes. Furthermore, ultrastructural analysis of these 4.1B mutants showed destabilization of CNS AGSJs at ∼1 year. We also discovered that the 4.1B locus is differentially expressed in the PNS and CNS, and generates multiple splice isoforms in the PNS, suggesting 4.1B may function differently in the PNS versus CNS. Together, our studies provide direct evidence that 4.1B plays a pivotal role in interactions between the paranodal AGSJs and axonal cytoskeleton, and that 4.1B is critically required for long-term maintenance of axonal domains in myelinated axons. [1]: #ref-20
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Septate Junctions are Required for Ommatidial Integrity and Blood-Eye Barrier Function in Drosophila
Developmental biology, 2008Co-Authors: Swati Banerjee, Roland J. Bainton, Nasima Mayer, Robert B. Beckstead, Manzoor A BhatAbstract:Abstract The anatomical organization of the Drosophila ommatidia is achieved by specification and contextual placement of photoreceptors, cone and pigment cells. The photoreceptors must be sealed from high ionic concentrations of the hemolymph by a barrier to allow phototransduction. In vertebrates, a blood–retinal barrier (BRB) is established by tight Junctions (TJs) present in the retinal pigment epithelium and endothelial membrane of the retinal vessels. In Drosophila ommatidia, the junctional organization and barrier formation is poorly understood. Here we report that Septate Junctions (SJs), the vertebrate analogs of TJs, are present in the adult ommatidia and are formed between and among the cone and pigment cells. We show that the localization of Neurexin IV (Nrx IV), a SJ-specific protein, coincides with the location of SJs in the cone and pigment cells. Somatic mosaic analysis of nrx IV null mutants shows that loss of Nrx IV leads to defects in ommatidial morphology and integrity. nrx IV hypomorphic allelic combinations generated viable adults with defective SJs and displayed a compromised blood–eye barrier (BEB) function. These findings establish that SJs are essential for ommatidial integrity and in creating a BEB around the ion and light sensitive photoreceptors. Our studies may provide clues towards understanding the vertebrate BEB formation and function.
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Organization and function of Septate Junctions
Cell Biochemistry and Biophysics, 2006Co-Authors: Swati Banerjee, Aurea D. Sousa, Manzoor A BhatAbstract:In most cell types, distinct forms of intercellular Junctions have been visualized at the ultrastructural level. Among these, the Septate Junctions are thought to seal the neighboring cells and thus to function as the paracellular barriers. The most extensively studied form of Septate Junctions, referred to as the pleated Septate Junctions, is ultrastructurally distinct with an electron-dense ladder-like arrangement of transverse septa present in invertebrates as well as vertebrates. In invertebrates, such as the fruit fly Drosophila melanogaster , Septate Junctions are present in all ectodermally derived epithelia, imaginal discs, and the nervous system. In vertebrates, Septate Junctions are present in the myelinated nerves at the paranodal interface between the myelin loops and the axonal membrane. In this review, we present an evolutionary perspective of Septate Junctions, especially their initial identification across phyla, and discuss many common features of their morphology, molecular organization, and functional similarities in invertebrates and vertebrates.
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Organization and function of Septate Junctions: An evolutionary perspective
Cell biochemistry and biophysics, 2006Co-Authors: Swati Banerjee, Aurea D. Sousa, Manzoor A BhatAbstract:In most cell types, distinct forms of intercellular Junctions have been visualized at the ultrastructural level. Among these, the Septate Junctions are thought to seal the neighboring cells and thus to function as the paracellular barriers. The most extensively studied form of Septate Junctions, referred to as the pleated Septate Junctions, is ultrastructurally distinct with an electron-dense ladder-like arrangement of transverse septa present in invertebrates as well as vertebrates. In invertebrates, such as the fruit fly Drosophila melanogaster, Septate Junctions are present in all ectodermally derived epithelia, imaginal discs, and the nervous system. In vertebrates, Septate Junctions are present in the myelinated nerves at the paranodal interface between the myelin loops and the axonal membrane. In this review, we present an evolutionary perspective of Septate Junctions, especially their initial identification across phyla, and discuss many common features of their morphology, molecular organization, and functional similarities in invertebrates and vertebrates.
Roland Le Borgne - One of the best experts on this subject based on the ideXlab platform.
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Interplay between Anakonda, Gliotactin, and M6 for Tricellular Junction Assembly and Anchoring of Septate Junctions in Drosophila Epithelium
Current biology : CB, 2020Co-Authors: Thomas Esmangart De Bournonville, Roland Le BorgneAbstract:In epithelia, tricellular Junctions (TCJs) serve as pivotal sites for barrier function and integration of both biochemical and mechanical signals [1-3]. In Drosophila, TCJs are composed of the transmembrane protein Sidekick at the adherens junction (AJ) level, which plays a role in cell-cell contact rearrangement [4-6]. At the Septate junction (SJ) level, TCJs are formed by Gliotactin (Gli) [7], Anakonda (Aka) [8, 9], and the Myelin proteolipid protein (PLP) M6 [10, 11]. Despite previous data on TCJ organization [12-14], TCJ assembly, composition, and links to adjacent bicellular Junctions (BCJs) remain poorly understood. Here, we have characterized the making of TCJs within the plane of adherens Junctions (tricellular adherens junction [tAJ]) and the plane of Septate Junctions (tricellular Septate junction [tSJ]) and report that their assembly is independent of each other. Aka and M6, whose localizations are interdependent, act upstream to localize Gli. In turn, Gli stabilizes Aka at tSJ. Moreover, tSJ components are not only essential at vertex, as we found that loss of tSJ integrity induces micron-length bicellular SJ (bSJ) deformations. This phenotype is associated with the disappearance of SJ components at tricellular contacts, indicating that bSJs are no longer connected to tSJs. Reciprocally, SJ components are required to restrict the localization of Aka and Gli at vertex. We propose that tSJs function as pillars to anchor bSJs to ensure the maintenance of tissue integrity in Drosophila proliferative epithelia.
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Coordination of Septate Junctions Assembly and Completion of Cytokinesis in Proliferative Epithelial Tissues.
Current biology : CB, 2018Co-Authors: Emeline Daniel, Vanessa J. Auld, Marion Daude, Irina Kolotuev, Kristi Charish, Roland Le BorgneAbstract:How permeability barrier function is maintained when epithelial cells divide is largely unknown. Here, we have investigated how the bicellular Septate Junctions (BSJs) and tricellular Septate Junctions (TSJs) are remodeled throughout completion of cytokinesis in Drosophila epithelia. We report that, following cytokinetic ring constriction, the midbody assembles, matures within SJs, and is displaced basally in two phases. In a first slow phase, the neighboring cells remain connected to the dividing cells by means of SJ-containing membrane protrusions pointing to the maturing midbody. Fluorescence recovery after photobleaching (FRAP) experiments revealed that SJs within the membrane protrusions correspond to the old SJs that were present prior to cytokinesis. In contrast, new SJs are assembled below the adherens Junctions and spread basally to build a new belt of SJs in a manner analogous to a conveyor belt. Loss of function of a core BSJ component, the Na+/K+-ATPase pump Nervana 2 subunit, revealed that the apical-to-basal spread of BSJs drives the basal displacement of the midbody. In contrast, loss of the TSJ protein Bark beetle indicated that remodeling of TSJs is rate limiting and slowed down midbody migration. In the second phase, once the belt of SJs is assembled, the basal displacement of the midbody is accelerated and ultimately leads to abscission. This last step is temporally uncoupled from the remodeling of SJs. We propose that cytokinesis in epithelia involves the coordinated polarized assembly and remodeling of SJs both in the dividing cell and its neighbors to ensure the maintenance of permeability barrier integrity in proliferative epithelia.
