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

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The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier. / Schell, Christoph; Rogg, Manuel; Suhm, Martina; Helmstädter, Martin; Sellung, Dominik; Yasuda-Yamahara, Mako; Kretz, Oliver; Küttner, Victoria; Suleiman, Hani; Kollipara, Laxmikanth; Zahedi, René P; Sickmann, Albert; Eimer, Stefan; Shaw, Andrey S; Kramer-Zucker, Albrecht G; Hirano-Kobayashi, Mariko; Abe, Takaya; Aizawa, Shinichi; Grahammer, Florian; Hartleben, Björn; Dengjel, Jörn; Huber, Tobias B.

In: P NATL ACAD SCI USA, Vol. 114, No. 23, 06.06.2017, p. E4621-E4630.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Schell, C, Rogg, M, Suhm, M, Helmstädter, M, Sellung, D, Yasuda-Yamahara, M, Kretz, O, Küttner, V, Suleiman, H, Kollipara, L, Zahedi, RP, Sickmann, A, Eimer, S, Shaw, AS, Kramer-Zucker, AG, Hirano-Kobayashi, M, Abe, T, Aizawa, S, Grahammer, F, Hartleben, B, Dengjel, J & Huber, TB 2017, 'The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier', P NATL ACAD SCI USA, vol. 114, no. 23, pp. E4621-E4630. https://doi.org/10.1073/pnas.1617004114

APA

Schell, C., Rogg, M., Suhm, M., Helmstädter, M., Sellung, D., Yasuda-Yamahara, M., Kretz, O., Küttner, V., Suleiman, H., Kollipara, L., Zahedi, R. P., Sickmann, A., Eimer, S., Shaw, A. S., Kramer-Zucker, A. G., Hirano-Kobayashi, M., Abe, T., Aizawa, S., Grahammer, F., ... Huber, T. B. (2017). The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier. P NATL ACAD SCI USA, 114(23), E4621-E4630. https://doi.org/10.1073/pnas.1617004114

Vancouver

Schell C, Rogg M, Suhm M, Helmstädter M, Sellung D, Yasuda-Yamahara M et al. The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier. P NATL ACAD SCI USA. 2017 Jun 6;114(23):E4621-E4630. https://doi.org/10.1073/pnas.1617004114

Bibtex

@article{7627e366fc704b01b60769bb95ab8721,
title = "The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier",
abstract = "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 matrix-dependent 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.",
keywords = "Journal Article",
author = "Christoph Schell and Manuel Rogg and Martina Suhm and Martin Helmst{\"a}dter and Dominik Sellung and Mako Yasuda-Yamahara and Oliver Kretz and Victoria K{\"u}ttner and Hani Suleiman and Laxmikanth Kollipara and Zahedi, {Ren{\'e} P} and Albert Sickmann and Stefan Eimer and Shaw, {Andrey S} and Kramer-Zucker, {Albrecht G} and Mariko Hirano-Kobayashi and Takaya Abe and Shinichi Aizawa and Florian Grahammer and Bj{\"o}rn Hartleben and J{\"o}rn Dengjel and Huber, {Tobias B}",
year = "2017",
month = jun,
day = "6",
doi = "10.1073/pnas.1617004114",
language = "English",
volume = "114",
pages = "E4621--E4630",
journal = "P NATL ACAD SCI USA",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "23",

}

RIS

TY - JOUR

T1 - The FERM protein EPB41L5 regulates actomyosin contractility and focal adhesion formation to maintain the kidney filtration barrier

AU - Schell, Christoph

AU - Rogg, Manuel

AU - Suhm, Martina

AU - Helmstädter, Martin

AU - Sellung, Dominik

AU - Yasuda-Yamahara, Mako

AU - Kretz, Oliver

AU - Küttner, Victoria

AU - Suleiman, Hani

AU - Kollipara, Laxmikanth

AU - Zahedi, René P

AU - Sickmann, Albert

AU - Eimer, Stefan

AU - Shaw, Andrey S

AU - Kramer-Zucker, Albrecht G

AU - Hirano-Kobayashi, Mariko

AU - Abe, Takaya

AU - Aizawa, Shinichi

AU - Grahammer, Florian

AU - Hartleben, Björn

AU - Dengjel, Jörn

AU - Huber, Tobias B

PY - 2017/6/6

Y1 - 2017/6/6

N2 - 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 matrix-dependent 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.

AB - 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 matrix-dependent 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.

KW - Journal Article

U2 - 10.1073/pnas.1617004114

DO - 10.1073/pnas.1617004114

M3 - SCORING: Journal article

C2 - 28536193

VL - 114

SP - E4621-E4630

JO - P NATL ACAD SCI USA

JF - P NATL ACAD SCI USA

SN - 0027-8424

IS - 23

ER -