Yurt, Coracle, Neurexin IV and the Na+,K+-ATPase form a novel group of epithelial polarity proteins

Laprise, Patrick; Lau, Kimberly; Harris, Kathryn P.; Silva-Gagliardi, Nancy F.; Paul, Sarah M.; Beronja, Slobodan; Beitel, Greg J.; McGlade, C. Jane; Tepaß, Ulrich

doi:10.1038/nature08067

Cited by 162 publications

(222 citation statements)

References 46 publications

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“…However, it was recently shown that some SJ components have a role in a newly identified phase of Drosophila epithelial polarity that occurs between stages 11 and 13 (Laprise et al 2009). Because of redundancy between SJ components involved in this polarity phase and the SJ component yrt, SJ proteins required for polarity can be identified only in a yrt zygotic mutant background (Laprise et al 2009). For example, single zygotic mutations in either the SJ gene Atpa or yrt show normal apical localization of Crb at stage 12 (Figure 7,D and E).…”

Section: Resultsmentioning

confidence: 99%

The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control

2010

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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, Kunekune, 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 barrierindependent 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 Kunekune 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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Section: Resultsmentioning

confidence: 99%

The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control

2010

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“…The EPB4.1 protein family is involved in cellular morphogenesis, and EPB41L5 was particularly investigated in terms of apicobasal polarity establishment via interaction with CRUMBS in early development (35,36). Previous work demonstrated that EPB41L5 was required during early embryo gastrulation, which seemed to be partially a result of EPB41L5-dependent FA modulation and cell-cell contact establishment via cadherins (37).…”

Section: Discussionmentioning

confidence: 99%

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

Schell

Rogg

Suhm

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Podocytes form the outer part of the glomerular filter, where they have to withstand enormous transcapillary filtration forces driving glomerular filtration. Detachment of podocytes from the glomerular basement membrane precedes most glomerular diseases. However, little is known about the regulation of podocyte adhesion in vivo. Thus, we systematically screened for podocyte-specific focal adhesome (FA) components, using genetic reporter models in combination with iTRAQ-based mass spectrometry. This approach led to the identification of FERM domain protein EPB41L5 as a highly enriched podocyte-specific FA component in vivo. Genetic deletion of Epb41l5 resulted in severe proteinuria, detachment of podocytes, and development of focal segmental glomerulosclerosis. Remarkably, by binding and recruiting the RhoGEF ARGHEF18 to the leading edge, EPB41L5 directly controls actomyosin contractility and subsequent maturation of focal adhesions, cell spreading, and migration. Furthermore, EPB41L5 controls matrixdependent outside-in signaling by regulating the focal adhesome composition. Thus, by linking extracellular matrix sensing and signaling, focal adhesion maturation, and actomyosin activation EPB41L5 ensures the mechanical stability required for podocytes at the kidney filtration barrier. Finally, a diminution of EPB41L5-dependent signaling programs appears to be a common theme of podocyte disease, and therefore offers unexpected interventional therapeutic strategies to prevent podocyte loss and kidney disease progression.focal adhesion | actomyosin | podocyte | FSGS

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“…De cette façon, nous avons établi l'existence d'une interaction génétique entre yurt et Atpa (codant la sous-unité alpha de la Na + , K + -ATPase) ainsi qu'entre yurt et Neurexin-IV [7]. Nos expériences d'interactions génétiques et la caractérisa-tion phénotypique des double mutants ont permis de mettre en lumière le rôle jusqu'alors insoupçonné de la Na + , K + -ATPase et de la Neurexine-IV dans la polarité épithéliale.…”

Section: Interactions Protéiques Coopératives Dans L'établissement Etunclassified

“…Nos expériences d'interactions génétiques et la caractérisa-tion phénotypique des double mutants ont permis de mettre en lumière le rôle jusqu'alors insoupçonné de la Na + , K + -ATPase et de la Neurexine-IV dans la polarité épithéliale. Par la suite, l'analyse des interactions génétiques du gène yurt a été étendue à des gènes encodant des protéines adaptatrices associées à la membrane basolatérale, ce qui a permis de démontrer que l'inactivation simultanée des gènes yurt et coracle entraîne une organisation apicale de la membrane plasmique au détriment du domaine basolatéral lors de l'organogenèse [7]. Ce phénotype est significativement aggravé lorsque les deux gènes sont inactivés simultanément plutôt qu'un seul de ces gènes, soit yurt, soit coracle.…”

Section: Interactions Protéiques Coopératives Dans L'établissement Etunclassified

Yurt, Coracle, Neurexin IV and the Na+,K+-ATPase form a novel group of epithelial polarity proteins

Cited by 162 publications

References 46 publications

The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control

The Drosophila Claudin Kune-kune Is Required for Septate Junction Organization and Tracheal Tube Size Control

The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

Maintien de la polarité épithéliale

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