Grahammer, Florian, Wigge, Christoph, Schell, Christoph, Kretz, Oliver, Patrakka, Jaakko, Schneider, Simon, Klose, Martin, Arnold, Sebastian J. ORCID: 0000-0002-2688-9210, Habermann, Anja ORCID: 0000-0003-3686-9050, Braeuniger, Ricarda, Rinschen, Markus M., Voelker, Linus, Bregenzer, Andreas, Rubbenstroth, Dennis, Boerries, Melanie, Kerjaschki, Dontscho, Miner, Jeffrey H., Walz, Gerd, Benzing, Thomas, Fornoni, Alessia, Frangakis, Achilleas S. and Huber, Tobias B. (2016). A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes. JCI Insight, 1 (9). ANN ARBOR: AMER SOC CLINICAL INVESTIGATION INC. ISSN 2379-3708

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Abstract

Vertebrate life critically depends on renal filtration and excretion of low molecular weight waste products. This process is controlled by a specialized cell-cell contact between podocyte foot processes: the slit diaphragm (SD). Using a comprehensive set of targeted KO mice of key SD molecules, we provided genetic, functional, and high-resolution ultrastructural data highlighting a concept of a flexible, dynamic, and multilayered architecture of the SD. Our data indicate that the mammalian SD is composed of NEPHRIN and NEPH1 molecules, while NEPH2 and NEPH3 do not participate in podocyte intercellular junction formation. Unexpectedly, homo-and heteromeric NEPHRIN/NEPH1 complexes are rarely observed. Instead, single NEPH1 molecules appear to form the lower part of the junction close to the glomerular basement membrane with a width of 23 nm, while single NEPHRIN molecules form an adjacent junction more apically with a width of 45 nm. In both cases, the molecules are quasiperiodically spaced 7 nm apart. These structural findings, in combination with the flexibility inherent to the repetitive Ig folds of NEPHRIN and NEPH1, indicate that the SD likely represents a highly dynamic cell-cell contact that forms an adjustable, nonclogging barrier within the renal filtration apparatus.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Grahammer, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wigge, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schell, ChristophUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kretz, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Patrakka, JaakkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schneider, SimonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klose, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arnold, Sebastian J.UNSPECIFIEDorcid.org/0000-0002-2688-9210UNSPECIFIED
Habermann, AnjaUNSPECIFIEDorcid.org/0000-0003-3686-9050UNSPECIFIED
Braeuniger, RicardaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Voelker, LinusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bregenzer, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rubbenstroth, DennisUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Boerries, MelanieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerjaschki, DontschoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Miner, Jeffrey H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Walz, GerdUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Benzing, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fornoni, AlessiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frangakis, Achilleas S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Huber, Tobias B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-272172
DOI: 10.1172/jci.insight.86177
Journal or Publication Title: JCI Insight
Volume: 1
Number: 9
Date: 2016
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Place of Publication: ANN ARBOR
ISSN: 2379-3708
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CONGENITAL NEPHROTIC SYNDROME; NEPHRIN GENE; DIAPHRAGM; ARCHITECTURE; COMPLEX; KIDNEY; SUBSTRUCTURE; EXPRESSION; FEATURES; FILTRINMultiple languages
Medicine, Research & ExperimentalMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/27217

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