The WD40-domain containing protein CORO2B is specifically enriched in glomerular podocytes and regulates the ventral actin cytoskeleton

M Rogg,F Grahammer,J Frimmel,M Yasuda-Yamahara,C Schell,M Helmstädter,P Dinse,T B Huber,O Schilling,D Sellung,A Abed,A C Conzelmann,M L Biniossek,O Kretz

doi:10.1038/s41598-017-15844-1

Abstract

Podocytes are highly specialized epithelial cells essentially required to establish and maintain the kidney filtration barrier. Due to their complex cellular architecture these cells rely on an elaborated cytoskeletal apparatus providing plasticity as well as adaptive adhesion properties to withstand significant physical filtration forces. However, our knowledge about podocyte specific components of the cytoskeletal machinery is still incomplete. Employing cross-analysis of various quantitative omics-data sets we identify the WD40-domain containing protein CORO2B as a podocyte enriched protein. Furthermore, we demonstrate the distinct localization pattern of CORO2B to the ventral actin cytoskeleton serving as a physical linkage module to cell-matrix adhesion sites. Analysis of a novel Coro2b knockout mouse revealed that CORO2B modulates stress response of podocytes in an experimental nephropathy model. Using quantitative focal adhesome proteomics we identify the recruitment of CFL1 via CORO2B to focal adhesions as an underlying mechanism. Thus, we describe CORO2B as a novel podocyte enriched protein influencing cytoskeletal plasticity and stress adaptation.

Highlights

Strain and the Differential Susceptibility of Podocyte-Specific Deletion of Myh[9] on Murine Models of Experimental Glomerulosclerosis and HIV Nephropathy
To discover novel podocyte specific regulators of the actin cytoskeleton, transcriptome and proteome datasets of isolated podocytes were re-analyzed for the expression of the coronin family of actin cytoskeleton regulators (Fig. 1a,b)
As control cells showed impaired spreading under treatment conditions, our findings suggest that CORO2B might serve as a susceptibility factor for a general stress response phenotype in cultured podocytes (Fig. 5m)

Summary

Introduction

Strain and the Differential Susceptibility of Podocyte-Specific Deletion of Myh[9] on Murine Models of Experimental Glomerulosclerosis and HIV Nephropathy. Uchio-Yamada, K. et al Tenc1-deficient mice develop glomerular disease in a strain-specific manner. M. et al Mutations in the INF2 gene account for a significant proportion of familial but not sporadic focal and segmental glomerulosclerosis. S. et al TRPC6 mutational analysis in a large cohort of patients with focal segmental glomerulosclerosis. B. et al Autophagy influences glomerular disease susceptibility and maintains podocyte homeostasis in aging mice. F. et al A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes. C. et al Podocyte-specific deletion of murine CXADR does not impair podocyte development, function or stress response.

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