A slit-diaphragm-associated protein network for dynamic control of renal filtration
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A slit-diaphragm-associated protein network for dynamic control of renal filtration. / 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; Göcmen, Burulca; Schwenk, Jochen; Schulte, Uwe; Huber, Tobias B; Fakler, Bernd; Grahammer, Florian.
In: NAT COMMUN, Vol. 13, No. 1, 28.10.2022, p. 6446.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A slit-diaphragm-associated protein network for dynamic control of renal filtration
AU - Kocylowski, Maciej K
AU - Aypek, Hande
AU - Bildl, Wolfgang
AU - Helmstädter, Martin
AU - Trachte, Philipp
AU - Dumoulin, Bernhard
AU - Wittösch, Sina
AU - Kühne, Lukas
AU - Aukschun, Ute
AU - Teetzen, Carolin
AU - Kretz, Oliver
AU - Gaal, Botond
AU - Kulik, Akos
AU - Antignac, Corinne
AU - Mollet, Geraldine
AU - Köttgen, Anna
AU - Göcmen, Burulca
AU - Schwenk, Jochen
AU - Schulte, Uwe
AU - Huber, Tobias B
AU - Fakler, Bernd
AU - Grahammer, Florian
N1 - © 2022. The Author(s).
PY - 2022/10/28
Y1 - 2022/10/28
N2 - 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.
AB - 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.
KW - Animals
KW - Diaphragm
KW - Proteomics
KW - Podocytes/metabolism
KW - Kidney Glomerulus
KW - Intercellular Junctions
KW - Mammals
U2 - 10.1038/s41467-022-33748-1
DO - 10.1038/s41467-022-33748-1
M3 - SCORING: Journal article
C2 - 36307401
VL - 13
SP - 6446
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -