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A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions

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A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions. / Rogg, Manuel; Maier, Jasmin I; Helmstädter, Martin; Sammarco, Alena; Kliewe, Felix; Kretz, Oliver; Weißer, Lisa; Van Wymersch, Clara; Findeisen, Karla; Koessinger, Anna L; Tsoy, Olga; Baumbach, Jan; Grabbert, Markus; Werner, Martin; Huber, Tobias B; Endlich, Nicole; Schilling, Oliver; Schell, Christoph.

In: CELLS-BASEL, Vol. 12, No. 13, 1795, 06.07.2023.

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

Harvard

Rogg, M, Maier, JI, Helmstädter, M, Sammarco, A, Kliewe, F, Kretz, O, Weißer, L, Van Wymersch, C, Findeisen, K, Koessinger, AL, Tsoy, O, Baumbach, J, Grabbert, M, Werner, M, Huber, TB, Endlich, N, Schilling, O & Schell, C 2023, 'A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions', CELLS-BASEL, vol. 12, no. 13, 1795. https://doi.org/10.3390/cells12131795

APA

Rogg, M., Maier, J. I., Helmstädter, M., Sammarco, A., Kliewe, F., Kretz, O., Weißer, L., Van Wymersch, C., Findeisen, K., Koessinger, A. L., Tsoy, O., Baumbach, J., Grabbert, M., Werner, M., Huber, T. B., Endlich, N., Schilling, O., & Schell, C. (2023). A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions. CELLS-BASEL, 12(13), [1795]. https://doi.org/10.3390/cells12131795

Vancouver

Rogg M, Maier JI, Helmstädter M, Sammarco A, Kliewe F, Kretz O et al. A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions. CELLS-BASEL. 2023 Jul 6;12(13). 1795. https://doi.org/10.3390/cells12131795

Bibtex

@article{65a25a5c57fc47dc81b659283776f5c1,
title = "A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions",
abstract = "Glomerular disease due to podocyte malfunction is a major factor in the pathogenesis of chronic kidney disease. Identification of podocyte-specific signaling pathways is therefore a prerequisite to characterizing relevant disease pathways and developing novel treatment approaches. Here, we employed loss of function studies for EPB41L5 (Yurt) as a central podocyte gene to generate a cell type-specific disease model. Loss of Yurt in fly nephrocytes caused protein uptake and slit diaphragm defects. Transcriptomic and proteomic analysis of human EPB41L5 knockout podocytes demonstrated impaired mechanotransduction via the YAP/TAZ signaling pathway. Further analysis of specific inhibition of the YAP/TAZ-TEAD transcription factor complex by TEADi led to the identification of ARGHAP29 as an EPB41L5 and YAP/TAZ-dependently expressed podocyte RhoGAP. Knockdown of ARHGAP29 caused increased RhoA activation, defective lamellipodia formation, and increased maturation of integrin adhesion complexes, explaining similar phenotypes caused by loss of EPB41L5 and TEADi expression in podocytes. Detection of increased levels of ARHGAP29 in early disease stages of human glomerular disease implies a novel negative feedback loop for mechanotransductive RhoA-YAP/TAZ signaling in podocyte physiology and disease.",
keywords = "Humans, Podocytes/metabolism, Adaptor Proteins, Signal Transducing/metabolism, YAP-Signaling Proteins, Mechanotransduction, Cellular, Integrins/metabolism, Proteomics, rhoA GTP-Binding Protein/metabolism, Signal Transduction, GTPase-Activating Proteins/metabolism, Membrane Proteins/metabolism",
author = "Manuel Rogg and Maier, {Jasmin I} and Martin Helmst{\"a}dter and Alena Sammarco and Felix Kliewe and Oliver Kretz and Lisa Wei{\ss}er and {Van Wymersch}, Clara and Karla Findeisen and Koessinger, {Anna L} and Olga Tsoy and Jan Baumbach and Markus Grabbert and Martin Werner and Huber, {Tobias B} and Nicole Endlich and Oliver Schilling and Christoph Schell",
year = "2023",
month = jul,
day = "6",
doi = "10.3390/cells12131795",
language = "English",
volume = "12",
journal = "CELLS-BASEL",
issn = "2073-4409",
publisher = "MDPI Multidisciplinary Digital Publishing Institute",
number = "13",

}

RIS

TY - JOUR

T1 - A YAP/TAZ-ARHGAP29-RhoA Signaling Axis Regulates Podocyte Protrusions and Integrin Adhesions

AU - Rogg, Manuel

AU - Maier, Jasmin I

AU - Helmstädter, Martin

AU - Sammarco, Alena

AU - Kliewe, Felix

AU - Kretz, Oliver

AU - Weißer, Lisa

AU - Van Wymersch, Clara

AU - Findeisen, Karla

AU - Koessinger, Anna L

AU - Tsoy, Olga

AU - Baumbach, Jan

AU - Grabbert, Markus

AU - Werner, Martin

AU - Huber, Tobias B

AU - Endlich, Nicole

AU - Schilling, Oliver

AU - Schell, Christoph

PY - 2023/7/6

Y1 - 2023/7/6

N2 - Glomerular disease due to podocyte malfunction is a major factor in the pathogenesis of chronic kidney disease. Identification of podocyte-specific signaling pathways is therefore a prerequisite to characterizing relevant disease pathways and developing novel treatment approaches. Here, we employed loss of function studies for EPB41L5 (Yurt) as a central podocyte gene to generate a cell type-specific disease model. Loss of Yurt in fly nephrocytes caused protein uptake and slit diaphragm defects. Transcriptomic and proteomic analysis of human EPB41L5 knockout podocytes demonstrated impaired mechanotransduction via the YAP/TAZ signaling pathway. Further analysis of specific inhibition of the YAP/TAZ-TEAD transcription factor complex by TEADi led to the identification of ARGHAP29 as an EPB41L5 and YAP/TAZ-dependently expressed podocyte RhoGAP. Knockdown of ARHGAP29 caused increased RhoA activation, defective lamellipodia formation, and increased maturation of integrin adhesion complexes, explaining similar phenotypes caused by loss of EPB41L5 and TEADi expression in podocytes. Detection of increased levels of ARHGAP29 in early disease stages of human glomerular disease implies a novel negative feedback loop for mechanotransductive RhoA-YAP/TAZ signaling in podocyte physiology and disease.

AB - Glomerular disease due to podocyte malfunction is a major factor in the pathogenesis of chronic kidney disease. Identification of podocyte-specific signaling pathways is therefore a prerequisite to characterizing relevant disease pathways and developing novel treatment approaches. Here, we employed loss of function studies for EPB41L5 (Yurt) as a central podocyte gene to generate a cell type-specific disease model. Loss of Yurt in fly nephrocytes caused protein uptake and slit diaphragm defects. Transcriptomic and proteomic analysis of human EPB41L5 knockout podocytes demonstrated impaired mechanotransduction via the YAP/TAZ signaling pathway. Further analysis of specific inhibition of the YAP/TAZ-TEAD transcription factor complex by TEADi led to the identification of ARGHAP29 as an EPB41L5 and YAP/TAZ-dependently expressed podocyte RhoGAP. Knockdown of ARHGAP29 caused increased RhoA activation, defective lamellipodia formation, and increased maturation of integrin adhesion complexes, explaining similar phenotypes caused by loss of EPB41L5 and TEADi expression in podocytes. Detection of increased levels of ARHGAP29 in early disease stages of human glomerular disease implies a novel negative feedback loop for mechanotransductive RhoA-YAP/TAZ signaling in podocyte physiology and disease.

KW - Humans

KW - Podocytes/metabolism

KW - Adaptor Proteins, Signal Transducing/metabolism

KW - YAP-Signaling Proteins

KW - Mechanotransduction, Cellular

KW - Integrins/metabolism

KW - Proteomics

KW - rhoA GTP-Binding Protein/metabolism

KW - Signal Transduction

KW - GTPase-Activating Proteins/metabolism

KW - Membrane Proteins/metabolism

U2 - 10.3390/cells12131795

DO - 10.3390/cells12131795

M3 - SCORING: Journal article

C2 - 37443829

VL - 12

JO - CELLS-BASEL

JF - CELLS-BASEL

SN - 2073-4409

IS - 13

M1 - 1795

ER -