A slit-diaphragm-associated protein network for dynamic control of renal filtration

Abstract: The filtration of blood in the kidney which is crucial for mammalian life is determined by the slit-diaphragm, a cell-cell junction between the foot processes of renal podocytes. The slit-diaphragm is thought to operate as final barrier or as molecular sensor of renal filtration. Using high-resolution proteomic analysis of slit-diaphragms affinity-isolated from rodent kidney, we show that the native slit-diaphragm is built from the junction-forming components Nephrin, Neph1 and Podocin and a co-assembled high-molecular weight network of proteins. The network constituents cover distinct classes of proteins including signaling-receptors, kinases/phosphatases, transporters and scaffolds. Knockout or knock-down of either the core components or the selected network constituents tyrosine kinase MER (MERTK), atrial natriuretic peptide-receptor C (ANPRC), integral membrane protein 2B (ITM2B), membrane-associated guanylate-kinase, WW and PDZ-domain-containing protein1 (MAGI1) and amyloid protein A4 resulted in target-specific impairment or disruption of the filtration process. Our results identify the slit-diaphragm as a multi-component system that is endowed with context-dependent dynamics via a co-assembled protein network

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature communications. - 13 (2022) , 6446, ISSN: 2041-1723

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2022
• Creator: Kocylowski, Maciej K. ; Aypek, Hande ; Bildl, Wolfgang ; Helmstädter, Martin ; Trachte, Philipp ; Dumoulin, Bernhard ; Wittösch, Sina ; Kühne, Lukas ; Aukschun, Ute ; Teetzen, Carolin ; Kretz, Oliver ; Gaal, Botond ; Kulik, Akos ; Antignac, Corinne ; Mollet, Geraldine ; Köttgen, Anna ; Uluvar, Burulc̨a ; Schwenk, Jochen ; Schulte, Uwe ; Huber, Tobias ; Fakler, Bernd ; Grahammer, Florian

Further information

• DOI: 10.1038/s41467-022-33748-1
• URN: urn:nbn:de:bsz:25-freidok-2307663
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 15.08.2025, 7:20 AM CEST