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

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-resoluti...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616960/
https://www.ncbi.nlm.nih.gov/pubmed/36307401
http://dx.doi.org/10.1038/s41467-022-33748-1
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author 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
author_facet 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
author_sort Kocylowski, Maciej K.
collection PubMed
description 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.
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spelling pubmed-96169602022-10-30 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 Nat Commun Article 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. Nature Publishing Group UK 2022-10-28 /pmc/articles/PMC9616960/ /pubmed/36307401 http://dx.doi.org/10.1038/s41467-022-33748-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
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
A slit-diaphragm-associated protein network for dynamic control of renal filtration
title A slit-diaphragm-associated protein network for dynamic control of renal filtration
title_full A slit-diaphragm-associated protein network for dynamic control of renal filtration
title_fullStr A slit-diaphragm-associated protein network for dynamic control of renal filtration
title_full_unstemmed A slit-diaphragm-associated protein network for dynamic control of renal filtration
title_short A slit-diaphragm-associated protein network for dynamic control of renal filtration
title_sort slit-diaphragm-associated protein network for dynamic control of renal filtration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9616960/
https://www.ncbi.nlm.nih.gov/pubmed/36307401
http://dx.doi.org/10.1038/s41467-022-33748-1
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