期刊
DEVELOPMENTAL CELL
卷 47, 期 6, 页码 741-+出版社
CELL PRESS
DOI: 10.1016/j.devcel.2018.11.011
关键词
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资金
- German Research Foundation (DFG) [CRC 1140, CRC 1192, CRC 992]
- Heisenberg program [HU 1016/5-1, HU 1016/8-1]
- European Research Council (ERC) [616891]
- H2020-IMI2 consortium BEAt-DKD [115974]
- BMBF (Bundesministerium fur Bildung und Forschung) [STOP-FSGS 01GM1518B, BMBF STOP-FSGS 01GM1518C]
- Excellence Initiative of the German Federal and State Governments (BIOSS)
- Excellence Initiative of the German Federal and State Governments (Freiburg Institute for Advanced Studies [FRIAS])
- Alexander von Humboldt Foundation
- German Society of Nephrology (DGFN)
- Else Kroner Fresenius Stiftung
- NAKSYS
- Matriglom [A_09]
- Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg
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.
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