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

Author

Listed:
  • Maciej K. Kocylowski

    (University of Freiburg)

  • Hande Aypek

    (University Medical Center Hamburg-Eppendorf)

  • Wolfgang Bildl

    (University of Freiburg)

  • Martin Helmstädter

    (University of Freiburg)

  • Philipp Trachte

    (University of Freiburg)

  • Bernhard Dumoulin

    (University Medical Center Hamburg-Eppendorf)

  • Sina Wittösch

    (University Medical Center Hamburg-Eppendorf)

  • Lukas Kühne

    (University of Freiburg)

  • Ute Aukschun

    (University of Freiburg)

  • Carolin Teetzen

    (University of Freiburg)

  • Oliver Kretz

    (University Medical Center Hamburg-Eppendorf)

  • Botond Gaal

    (University of Freiburg
    University of Debrecen)

  • Akos Kulik

    (University of Freiburg)

  • Corinne Antignac

    (Paris Descartes University)

  • Geraldine Mollet

    (Paris Descartes University)

  • Anna Köttgen

    (University of Freiburg)

  • Burulca Göcmen

    (University of Freiburg)

  • Jochen Schwenk

    (University of Freiburg)

  • Uwe Schulte

    (University of Freiburg)

  • Tobias B. Huber

    (University Medical Center Hamburg-Eppendorf)

  • Bernd Fakler

    (University of Freiburg
    Signalling Research Centres BIOSS and CIBSS)

  • Florian Grahammer

    (University Medical Center Hamburg-Eppendorf)

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.

Suggested Citation

  • Maciej K. Kocylowski & Hande Aypek & Wolfgang Bildl & Martin Helmstädter & Philipp Trachte & Bernhard Dumoulin & Sina Wittösch & Lukas Kühne & Ute Aukschun & Carolin Teetzen & Oliver Kretz & Botond Ga, 2022. "A slit-diaphragm-associated protein network for dynamic control of renal filtration," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33748-1
    DOI: 10.1038/s41467-022-33748-1
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    References listed on IDEAS

    as
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