Arp3 controls the podocyte architecture at the kidney filtration barrier

Schell, Christoph; Sabass, Benedikt; Helmstaedter, Martin; Geist, Felix; Abed, Ahmed; Yasuda-Yamahara, Mako; Sigle, August; Maier, Jasmin I.; Grahammer, Florian; Siegerist, Florian; Artelt, Nadine; Endlich, Nicole; Kerjaschki, Dontscho; Arnold, Hans-Henning; Dengjel, Jörn; Rogg, Manuel; Huber, Tobias B.

doi:10.1016/j.devcel.2018.11.011

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Arp3 controls the podocyte architecture at the kidney filtration barrier

Schell, Christoph Institute of Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg, Germany
Sabass, Benedikt Institute of Complex Systems-2, Forschungszentrum Jülich, Germany
Helmstaedter, Martin Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Geist, Felix Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Abed, Ahmed Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Yasuda-Yamahara, Mako Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - Department of Medicine, Shiga University of Medical Science, Otsu, Shiga Japan
Sigle, August Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Maier, Jasmin I. Institute of Surgical Pathology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Grahammer, Florian Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Siegerist, Florian Department of Anatomy and Cell Biology, University Medicine Greifswald, Germany
Artelt, Nadine Department of Anatomy and Cell Biology, University Medicine Greifswald, Germany
Endlich, Nicole Department of Anatomy and Cell Biology, University Medicine Greifswald, Germany
Kerjaschki, Dontscho Department of Pathology, Medical University of Vienna, Austria
Arnold, Hans-Henning Cell and Molecular Biology, Technical University of Braunschweig, Germany
Dengjel, Jörn BIOSS Center for Biological Signaling Studies, Albert-Ludwigs-University Freiburg, Germany - Department of Biology, University of Fribourg, Switzerland - Department of Dermatology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany
Rogg, Manuel Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany -
Huber, Tobias B. Department of Medicine IV, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Germany - Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany - BIOSS Center for Biological Signaling Studies, Albert-Ludwigs-University Freiburg, Germany -

17.12.2018

Published in:

Developmental Cell. - 2018, vol. 47, no. 6, p. 741-757.e8

English Podocytes, highly specialized epithelial cells, build the outer part of the kidney filtration barrier and withstand high mechanical forces through a complex network of cellular protrusions. Here, we show that Arp2/3-dependent actin polymerization controls actomyosin contractility and focal adhesion maturation of podocyte protrusions and thereby regulates formation, maintenance, and capacity to adapt to mechanical requirements of the filtration barrier. We find that N-WASP-Arp2/3 define the development of complex arborized podocyte protrusions in vitro and in vivo. Loss of dendritic actin networks results in a pronounced activation of the actomyosin cytoskeleton and the generation of over-maturated but less efficient adhesion, leading to detachment of podocytes. Our data provide a model to explain podocyte protrusion morphology and their mechanical stability based on a tripartite relationship between actin polymerization, contractility, and adhesion.

Faculty

Faculté des sciences et de médecine

Department

Département de Biologie

Language