EPB41L5 controls podocyte extracellular matrix assembly by adhesome-dependent force transmission

Maier, Jasmin I.; Rogg, Manuel; Helmstaedter, Martin; Sammarco, Alena; Schilling, Oliver; Sabass, Benedikt; Miner, Jeffrey H.; Dengjel, Joern; Walz, Gerd; Werner, Martin; Huber, Tobias B. und Schell, Christoph (2021): EPB41L5 controls podocyte extracellular matrix assembly by adhesome-dependent force transmission. In: Cell Reports, Bd. 34, Nr. 12, 108883

Abstract

The integrity of the kidney filtration barrier essentially relies on the balanced interplay of podocytes and the glomerular basementmembrane (GBM). Here, we show by analysis of in vitro and in vivo models that a loss of the podocyte-specific FERM-domain protein EPB41L5 results in impaired extracellular matrix (ECM) assembly. By using quantitative proteomics analysis of the secretome and matrisome, we demonstrate a shift in ECM composition characterized by diminished deposition of core GBM components, such as LAMA5. Integrin adhesome proteomics reveals that EPB41L5 recruits PDLIM5 and ACTN4 to integrin adhesion complexes (IACs). Consecutively, EPB41L5 knockout podocytes show insufficientmaturation of integrin adhesion sites, which translates into impaired force transmission and ECM assembly. These observations build the framework for a model in which EPB41L5 functions as a cell-type-specific regulator of the podocyte adhesome and controls a localized adaptive module in order to prevent podocyte detachment and thereby ensures GBM integrity.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Tiermedizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2211-1247
• Sprache: Englisch