EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial–mesenchymal transition

Hirano, Mariko; Hashimoto, Shigeru; Yonemura, Shigenobu; Sabe, Hisataka; Aizawa, Shinichi

doi:10.1083/jcb.200712086

Cited by 83 publications

(112 citation statements)

References 48 publications

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“…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). On the basis of our observations, we here propose that EPB41L5 mainly influences the maturational phase of FAs, implicating that decreased tension or traction might attribute for the detachment of podocytes, as evidenced in the EPB41L5 knockout model (Figs.…”

Section: Discussionsupporting

confidence: 77%

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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Section: Discussionsupporting

confidence: 77%

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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“…Ngn3-positive cells are still epithelial cells expressing Ecadherin. E-cadherin is known to be a very stable protein and has to be regulated both at the protein and the transcriptional levels to efficiently promote EMT (Arnold et al, 2008;Hirano et al, 2008;Zahn et al, 2008). Therefore, subtle changes in E-cadherin may have already started but are not detectable yet.…”

Section: Discussionmentioning

confidence: 99%

“…6B). In the absence of known pancreas progenitor cell lines, this epithelial cell line was chosen based on its robust endogenous E-cadherin expression and its common use as an EMT model (Miettinen et al, 2000;Hirano et al, 2008). Known repressors of E-cadherin such as Snail1 and Snail2 could efficiently repress transcription of E-cadherin when compared with control transfection (Fig.…”

Section: E-cadherin Is Transcriptionally Regulated In Endocrine Cellsmentioning

confidence: 99%

Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development

Gouzi

Kim

Katsumoto

et al. 2011

Developmental Dynamics

141

124

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During development, pancreatic endocrine cells are specified within the pancreatic epithelium. They subsequently delaminate out of the epithelium and cluster in the mesenchyme to form the islets of Langerhans. Neurogenin3 (Ngn3) is a transcription factor required for the differentiation of all endocrine cells and we investigated its role in their delamination. We observed in the mouse pancreas that most Ngn3-positive cells have lost contact with the lumen of the epithelium, showing that the delamination from the progenitor layer is initiated in endocrine progenitors. Subsequently, in both mouse and chick newly born endocrine cells at the periphery of the epithelium strongly decrease E-cadherin, break-down the basal lamina and cluster into islets of Langerhans. Repression of E-cadherin is sufficient to promote delamination from the epithelium. We further demonstrate that Ngn3 indirectly controls Snail2 protein expression post-transcriptionally to repress E-cadherin. In the chick embryo, Ngn3 independently controls epithelium delamination and differentiation programs. Developmental Dynamics 240:589-604,

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“…This indirect effect of p120cate-nin could be cell-type specific as the expression of a p120catenin mutant unable to regulate RhoA in endothelial cells has no effect on VE-cadherin endocytosis [52]. Finally, cadherin-bound p120catenin associates with FERM-domain containing proteins (EPB4125 and FRMD5) that modulate cadherin stability at the plasma membrane [61,62].…”

Section: Membrane-associated P120catenin and The Regulation Of Adherementioning

confidence: 99%

p120catenin alteration in cancer and its role in tumour invasion

Péglion

Etienne-Manneville

2013

Phil. Trans. R. Soc. B

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Since its discovery in 1989 as a substrate of the Src oncogene, p120catenin has been revealed as an important player in cancer initiation and tumour dissemination. p120catenin regulates a wide range of cellular processes such as cell–cell adhesion, cell polarity and cell proliferation and plays a pivotal role in morphogenesis, inflammation and innate immunity. The pleiotropic effects of p120catenin rely on its interactions with numerous partners such as classical cadherins at the plasma membrane, Rho-GTPases and microtubules in the cytosol and transcriptional modulators in the nucleus. Alterations of p120catenin in cancer not only concern its expression level but also its intracellular localization and can lead to both pro-invasive and anti-invasive effects. This review focuses on the p120catenin-mediated pathways involved in cell migration and invasion and discusses the potential consequences of major cancer-related p120catenin alterations with respect to tumour spread.

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EPB41L5 functions to post-transcriptionally regulate cadherin and integrin during epithelial–mesenchymal transition

Cited by 83 publications

References 48 publications

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

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

Neurogenin3 initiates stepwise delamination of differentiating endocrine cells during pancreas development

p120catenin alteration in cancer and its role in tumour invasion

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