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

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.

AIF1L regulates actomyosin contractility and filopodial extensions in human podocytes

“…Context dependent requirements are also reflected by a cell type specific composition of the cytoskeleton, as demonstrated by others and us (e.g. SYNPO, ARHGAP24 or CORO2B –[ 17 , 31 , 32 ]). Proteomic analysis for selectively or highly enriched expression of cytoskeletal proteins led to the identification of AIF1L in glomerular epithelial cells ( Fig 1 ).…”

“…Measurement of focal adhesions was performed as described previously [ 17 ]. In brief, human immortalized podocytes were cultured on collagen IV coated glass coverslips and immunofluorescence staining was performed for the focal adhesion component PAXILLIN.…”

Coro2b, a podocyte protein downregulated in human diabetic nephropathy, is involved in the development of protamine sulphate-induced foot process effacement

“…As Coro2b was recently reported to localize to focal adhesions at the basal aspects of podocyte foot processes 9,10 , we analyzed in more detail the distribution of Coro2b in podocytes. We applied an optical clearing protocol to a mouse kidney expressing tdtomato in podocytes to perform high resolution imaging.…”

“…While this manuscript was under preparation, Rogg et al . published a paper on Coro2b in human and mouse podocytes 9 . They performed detailed studies in cultured podocytes, and showed that constitutive KO mice have normal glomerular structure and function but are partially protected from doxorubicin-induced glomerular injury.…”

When Actin is Not Actin’ Like It Should: A New Category of Distinct Primary Immunodeficiency Disorders

“…It has been described that coronin-1A can directly interact with the ARP2/3 complex [86], is present at the leading edge during chemotaxis [78, 87], and plays a role in phagocytosis [87] and signal transduction [88]. Class II includes coronin-4 and coronin-5 (also called 2A and 2B), involved in focal adhesion turnover, reorganization of the cytoskeleton, and cell migration [89, 90]. The class III coronin-7 has an unusual structure and plays a role in Golgi morphology maintenance [91, 92].…”