The Experts below are selected from a list of 279 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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Echinoid regulates tracheal morphology and fusion cell fate in Drosophila
2015Co-Authors: Caroline Laplante, Greg J. Beitel, Sarah M. Paul, Laura A. NilsonAbstract:Morphogenesis of the Drosophila embryonic trachea involves a stereotyped pattern of epithelial tube branching and fusion. Here, we report unexpected phenotypes resulting from maternal and zygotic (M/Z) loss of the homophilic cell adhesion molecule Echinoid (Ed), as well as the subcellular localization of Ed in the trachea. edM/Z embryos have convoluted trachea reminiscent of Septate Junction (SJ) and luminal matrix mutants. However, Ed does not localize to SJs, and edM/Z embryos have intact SJs and show normal luminal accumulation of the matrix-modifying protein Vermiform. Surprisingly, tracheal length is not increased in edM/Z mutants, but a previously undescribed combination of reduced intersegmental spacing and deep epidermal grooves produces a convoluted tracheal phenotype. In addition, edM/Z mutants have unique fusion defects involving supernumerary fusion cells, ectopic fusion events and atypical branch breaks. Tracheal-specific expression of Ed rescues these fusion defects, indicating that Ed acts in trachea to control fusion cell fate
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The Drosophila claudin Kune-kune is required for Septate Junction organization and tracheal tube size control
Genetics, 2010Co-Authors: Kevin S. Nelson, Mikio Furuse, Greg J. BeitelAbstract:The vertebrate tight Junction is a critical claudin-based cell–cell Junction that functions to prevent free paracellular diffusion between epithelial cells. In Drosophila, this barrier is provided by the Septate Junction, which, despite being ultrastructurally distinct from the vertebrate tight Junction, also contains the claudin-family proteins Megatrachea and Sinuous. Here we identify a third Drosophila claudin, Kune-kune, that localizes to Septate Junctions and is required for Junction organization and paracellular barrier function, but not for apical-basal polarity. In the tracheal system, Septate Junctions have a barrier-independent function that promotes lumenal secretion of Vermiform and Serpentine, extracellular matrix modifier proteins that are required to restrict tube length. As with Sinuous and Megatrachea, loss of Kune-kune prevents this secretion and results in overly elongated tubes. Embryos lacking all three characterized claudins have tracheal phenotypes similar to any single mutant, indicating that these claudins act in the same pathway controlling tracheal tube length. However, we find that there are distinct requirements for these claudins in epithelial Septate Junction formation. Megatrachea is predominantly required for correct localization of Septate Junction components, while Sinuous is predominantly required for maintaining normal levels of Septate Junction proteins. Kune-kune is required for both localization and levels. Double- and triple-mutant combinations of Sinuous and Megatrachea with Kune-kune resemble the Kune-kune single mutant, suggesting that Kune-kune has a more central role in Septate Junction formation than either Sinuous or Megatrachea.
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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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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.
Niraj K. Nirala - One of the best experts on this subject based on the ideXlab platform.
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The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila.
Stem cell reports, 2020Co-Authors: Hsi-ju Chen, Niraj K. NiralaAbstract:Tight Junctions in mammals and Septate Junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth Septate Junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth Septate Junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and Septate Junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh causes Yorkie-dependent expression of the JAK-STAT pathway ligand Upd3, which in turn promotes proliferation of intestinal stem cells. Snakeskin and Mesh form a complex with each other, with other Septate Junction proteins and with Yorkie. Therefore, the Snakeskin-Mesh complex has both barrier and signaling function to maintain stem cell-mediated tissue homeostasis.
Mikio Furuse - One of the best experts on this subject based on the ideXlab platform.
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A novel membrane protein Hoka regulates Septate Junction organization and stem cell homeostasis in the Drosophila gut
2020Co-Authors: Yasushi Izumi, Kyoko Furuse, Mikio FuruseAbstract:Smooth Septate Junctions (sSJs) regulate the paracellular transport in the intestinal and renal system in arthropods. In Drosophila, the organization and physiological function of sSJs are regulated by at least three sSJ-specific membrane proteins: Ssk, Mesh, and Tsp2A. Here, we report a novel sSJ membrane protein Hoka, which has a single membrane-spanning segment with a short extracellular region having 13-amino acids, and a cytoplasmic region with three repeats of the Tyr-Thr-Pro-Ala motif. The larval midgut in hoka-mutants shows a defect in sSJ structure. Hoka forms a complex with Ssk, Mesh, and Tsp2A and is required for the correct localization of these proteins to sSJs. Knockdown of hoka in the adult midgut leads to intestinal barrier dysfunction, stem cell overproliferation, and epithelial tumors. In hoka-knockdown midguts, aPKC is up-regulated in the cytoplasm and the apical membrane of epithelial cells. The depletion of aPKC and yki in hoka-knockdown midguts results in reduced stem cell overproliferation. These findings indicate that Hoka cooperates with the sSJ-proteins Ssk, Mesh, and Tsp2A to organize sSJs, and is required for maintaining intestinal stem cell homeostasis through the regulation of aPKC and Yki activities in the Drosophila midgut. Summary statementDepletion of hoka, a gene encoding a novel Septate Junction protein, from the Drosophila midgut results in the disruption of Septate Junctions, intestinal barrier dysfunction, stem cell overproliferation, and epithelial tumors.
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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.
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A novel protein complex, Mesh-Ssk, is required for Septate Junction formation in the Drosophila midgut.
Journal of Cell Science, 2012Co-Authors: Yasushi Izumi, Yuichi Yanagihashi, Mikio FuruseAbstract:Septate Junctions (SJs) are specialized intercellular Junctions that restrict the free diffusion of solutes through the paracellular route in invertebrate epithelia. In arthropods, two morphologically different types of SJs have been reported: pleated SJs and smooth SJs (sSJs), which are found in ectodermally and endodermally derived epithelia, respectively. However, the molecular and functional differences between these SJ types have not been fully elucidated. Here, we report that a novel sSJ-specific component, a single-pass transmembrane protein, which we term 'Mesh' (encoded by CG31004), is highly concentrated in Drosophila sSJs. Compromised mesh expression causes defects in the organization of sSJs, in the localizations of other sSJ proteins, and in the barrier function of the midgut. Ectopic expression of Mesh in cultured cells induces cell-cell adhesion. Mesh forms a complex with Ssk, another sSJ-specific protein, and these proteins are mutually interdependent for their localization. Thus, a novel protein complex comprising Mesh and Ssk has an important role in sSJ formation and in intestinal barrier function in Drosophila.
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The Drosophila claudin Kune-kune is required for Septate Junction organization and tracheal tube size control
Genetics, 2010Co-Authors: Kevin S. Nelson, Mikio Furuse, Greg J. BeitelAbstract:The vertebrate tight Junction is a critical claudin-based cell–cell Junction that functions to prevent free paracellular diffusion between epithelial cells. In Drosophila, this barrier is provided by the Septate Junction, which, despite being ultrastructurally distinct from the vertebrate tight Junction, also contains the claudin-family proteins Megatrachea and Sinuous. Here we identify a third Drosophila claudin, Kune-kune, that localizes to Septate Junctions and is required for Junction organization and paracellular barrier function, but not for apical-basal polarity. In the tracheal system, Septate Junctions have a barrier-independent function that promotes lumenal secretion of Vermiform and Serpentine, extracellular matrix modifier proteins that are required to restrict tube length. As with Sinuous and Megatrachea, loss of Kune-kune prevents this secretion and results in overly elongated tubes. Embryos lacking all three characterized claudins have tracheal phenotypes similar to any single mutant, indicating that these claudins act in the same pathway controlling tracheal tube length. However, we find that there are distinct requirements for these claudins in epithelial Septate Junction formation. Megatrachea is predominantly required for correct localization of Septate Junction components, while Sinuous is predominantly required for maintaining normal levels of Septate Junction proteins. Kune-kune is required for both localization and levels. Double- and triple-mutant combinations of Sinuous and Megatrachea with Kune-kune resemble the Kune-kune single mutant, suggesting that Kune-kune has a more central role in Septate Junction formation than either Sinuous or Megatrachea.
Hsi-ju Chen - One of the best experts on this subject based on the ideXlab platform.
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The Snakeskin-Mesh Complex of Smooth Septate Junction Restricts Yorkie to Regulate Intestinal Homeostasis in Drosophila.
Stem cell reports, 2020Co-Authors: Hsi-ju Chen, Niraj K. NiralaAbstract:Tight Junctions in mammals and Septate Junctions in insects are essential for epithelial integrity. We show here that, in the Drosophila intestine, smooth Septate Junction proteins provide barrier and signaling functions. During an RNAi screen for genes that regulate adult midgut tissue growth, we found that loss of two smooth Septate Junction components, Snakeskin and Mesh, caused a hyperproliferation phenotype. By examining epitope-tagged endogenous Snakeskin and Mesh, we demonstrate that the two proteins are present in the cytoplasm of differentiating enteroblasts and in cytoplasm and Septate Junctions of mature enterocytes. In both enteroblasts and enterocytes, loss of Snakeskin and Mesh causes Yorkie-dependent expression of the JAK-STAT pathway ligand Upd3, which in turn promotes proliferation of intestinal stem cells. Snakeskin and Mesh form a complex with each other, with other Septate Junction proteins and with Yorkie. Therefore, the Snakeskin-Mesh complex has both barrier and signaling function to maintain stem cell-mediated tissue homeostasis.
Christian Klämbt - One of the best experts on this subject based on the ideXlab platform.
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Non-Cell-Autonomous Function of the GPI-Anchored Protein Undicht during Septate Junction Assembly.
Cell reports, 2019Co-Authors: Johanna Petri, Mubarak Hussain Syed, Simone Rey, Christian KlämbtAbstract:Summary Occluding cell-cell Junctions are pivotal during the development of many organs. One example is Septate Junction (SJ) strands, which are found in vertebrates and invertebrates. Although several proteins have been identified that are responsible for Septate Junction formation in Drosophila, it is presently unclear how these structures are formed or how they are positioned in a coordinated manner between two neighboring cells and within the tissue. Here, we identified a GPI-anchored protein called Undicht required for Septate Junction formation. Clonal analysis and rescue experiments show that Undicht acts in a non-cell-autonomous manner. It can be released from the plasma membrane by the proteolytic activity of two related ADAM10-like proteases, Kuzbanian and Kuzbanian-like. We propose that juxtacrine function of Undicht coordinates the formation of Septate Junction strands on two directly neighboring cells, whereas paracrine activity of Undicht controls the formation of occluding Junctions within a tissue.
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Non-Cell-Autonomous Function of the GPI-Anchored Protein Undicht during Septate Junction Assembly
Elsevier, 2019Co-Authors: Johanna Petri, Mubarak Hussain Syed, Simone Rey, Christian KlämbtAbstract:Summary: Occluding cell-cell Junctions are pivotal during the development of many organs. One example is Septate Junction (SJ) strands, which are found in vertebrates and invertebrates. Although several proteins have been identified that are responsible for Septate Junction formation in Drosophila, it is presently unclear how these structures are formed or how they are positioned in a coordinated manner between two neighboring cells and within the tissue. Here, we identified a GPI-anchored protein called Undicht required for Septate Junction formation. Clonal analysis and rescue experiments show that Undicht acts in a non-cell-autonomous manner. It can be released from the plasma membrane by the proteolytic activity of two related ADAM10-like proteases, Kuzbanian and Kuzbanian-like. We propose that juxtacrine function of Undicht coordinates the formation of Septate Junction strands on two directly neighboring cells, whereas paracrine activity of Undicht controls the formation of occluding Junctions within a tissue. : Petri et al. show that the Drosophila Undicht protein is essential for Septate Junction formation. Undicht can be released from the plasma membrane by ADAM10-like proteases to coordinate the formation of Septate Junctions within a tissue. Keywords: Drosophila, Septate Junction, blood-brain barrier, ADAM10-like proteases, Undicht, GPI ancho
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The Drosophila Blood-Brain Barrier Adapts to Cell Growth by Unfolding of Pre-existing Septate Junctions
Developmental cell, 2018Co-Authors: Felix Babatz, Elke Naffin, Christian KlämbtAbstract:The blood-brain barrier is crucial for nervous system function. It is established early during development and stays intact during growth of the brain. In invertebrates, Septate Junctions are the occluding Junctions of this barrier. Here, we used Drosophila to address how Septate Junctions grow during larval stages when brain size increases dramatically. We show that Septate Junctions are preassembled as long, highly folded strands during embryonic stages, connecting cell vertices. During subsequent cell growth, these corrugated strands are stretched out and stay intact during larval life with very little protein turnover. The G-protein coupled receptor Moody orchestrates the continuous organization of Junctional strands in a process requiring F-actin. Consequently, in moody mutants, Septate Junction strands cannot properly stretch out during cell growth. To compensate for the loss of blood-brain barrier function, moody mutants form interdigitating cell-cell protrusions, resembling the evolutionary ancient barrier type found in primitive vertebrates or invertebrates such as cuttlefish.
