AIF1L regulates actomyosin contractility and filopodial extensions in human podocytes

Mako Yasuda-Yamahara; Manuel Rogg; Kosuke Yamahara; Jasmin I Maier; Tobias B Huber; Christoph Schell

doi:10.1371/journal.pone.0200487

AIF1L regulates actomyosin contractility and filopodial extensions in human podocytes

PLoS One. 2018 Jul 12;13(7):e0200487. doi: 10.1371/journal.pone.0200487. eCollection 2018.

Authors

Mako Yasuda-Yamahara^{1

2}, Manuel Rogg¹, Kosuke Yamahara^{1

2}, Jasmin I Maier^{1

3}, Tobias B Huber^{1

4

5}, Christoph Schell^{1

3

6}

Affiliations

¹ Department of Medicine IV, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
³ Institute for Surgical Pathology, University Medical Center Freiburg, Freiburg, Germany.
⁴ BIOSS Center for Biological Signalling Studies, Albert-Ludwigs-University Freiburg, Freiburg, Germany.
⁵ Department of Medicine III, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁶ Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Abstract

Podocytes are highly-specialized epithelial cells essentially required for the generation and the maintenance of the kidney filtration barrier. This elementary function is directly based on an elaborated cytoskeletal apparatus establishing a complex network of primary and secondary processes. Here, we identify the actin-bundling protein allograft-inflammatory-inhibitor 1 like (AIF1L) as a selectively expressed podocyte protein in vivo. We describe the distinct subcellular localization of AIF1L to actin stress fibers, focal adhesion complexes and the nuclear compartment of podocytes in vitro. Genetic deletion of AIF1L in immortalized human podocytes resulted in an increased formation of filopodial extensions and decreased actomyosin contractility. By the use of SILAC based quantitative proteomics analysis we describe the podocyte specific AIF1L interactome and identify several components of the actomyosin machinery such as MYL9 and UNC45A as potential AIF1L interaction partners. Together, these findings indicate an involvement of AIF1L in the stabilization of podocyte morphology by titrating actomyosin contractility and membrane dynamics.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Actomyosin / metabolism*
Calcium-Binding Proteins / metabolism*
Cells, Cultured
Focal Adhesions / metabolism
Humans
Intracellular Signaling Peptides and Proteins / metabolism
Microfilament Proteins / metabolism*
Myosin Light Chains / metabolism
Podocytes / cytology
Podocytes / metabolism*
Pseudopodia / metabolism*
Stress Fibers / metabolism

Substances

AIF1L protein, human
Calcium-Binding Proteins
Intracellular Signaling Peptides and Proteins
MYL9 protein, human
Microfilament Proteins
Myosin Light Chains
UNC45A protein, human
Actomyosin

Grants and funding

This study was supported by the German Research Foundation (DFG): CRC 1140 (to TBH) and CRC 992 (to TBH), Heisenberg program (to TBH), and HU 1016/8-1 (to TBH); by the European Research Council (ERC grant to TBH) and by the H2020-IMI2 consortium BEAt-DKD (115974; to TBH); by the BMBF STOP-FSGS 01GM1518C (to TBH); by the MSD Life Science Foundation, Public Interest Incorporated Foundation and by the Uehara Memorial Foundation (to MY); by the Excellence Initiative of the German Federal and State Governments (BIOSS to TBH and CS) and the Freiburg Institute for Advanced Studies (FRIAS) (to TBH); the German Society of Nephrology DGFN (to CS), by the Else Kröner Fresenius Stiftung, NAKSYS (to MR, CS and TBH), Else Kröner-Fresenius-Stiftung-2018_A09 (to CS) and by the Berta-Ottenstein Programme, Faculty of Medicine, University of Freiburg (to CS). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.