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Sci Rep ; 7(1): 15910, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29162887

RESUMO

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.


Assuntos
Citoesqueleto de Actina/metabolismo , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/metabolismo , Podócitos/metabolismo , Repetições WD40 , Citoesqueleto de Actina/ultraestrutura , Actinas/metabolismo , Animais , Cofilina 1/metabolismo , Adesões Focais/metabolismo , Adesões Focais/ultraestrutura , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/genética , Modelos Biológicos , Podócitos/ultraestrutura , Estresse Fisiológico , Análise de Sobrevida
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