A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes
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A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes. / Grahammer, Florian; Wigge, Christoph; Schell, Christoph; Kretz, Oliver; Patrakka, Jaakko; Schneider, Simon; Klose, Martin; Arnold, Sebastian J; Habermann, Anja; Bräuniger, Ricarda; Rinschen, Markus M; Völker, Linus; Bregenzer, Andreas; Rubbenstroth, Dennis; Boerries, Melanie; Kerjaschki, Dontscho; Miner, Jeffrey H; Walz, Gerd; Benzing, Thomas; Fornoni, Alessia; Frangakis, Achilleas S; Huber, Tobias B.
in: JCI INSIGHT, Jahrgang 1, Nr. 9, 16.06.2016.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A flexible, multilayered protein scaffold maintains the slit in between glomerular podocytes
AU - Grahammer, Florian
AU - Wigge, Christoph
AU - Schell, Christoph
AU - Kretz, Oliver
AU - Patrakka, Jaakko
AU - Schneider, Simon
AU - Klose, Martin
AU - Arnold, Sebastian J
AU - Habermann, Anja
AU - Bräuniger, Ricarda
AU - Rinschen, Markus M
AU - Völker, Linus
AU - Bregenzer, Andreas
AU - Rubbenstroth, Dennis
AU - Boerries, Melanie
AU - Kerjaschki, Dontscho
AU - Miner, Jeffrey H
AU - Walz, Gerd
AU - Benzing, Thomas
AU - Fornoni, Alessia
AU - Frangakis, Achilleas S
AU - Huber, Tobias B
PY - 2016/6/16
Y1 - 2016/6/16
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1172/jci.insight.86177
DO - 10.1172/jci.insight.86177
M3 - SCORING: Journal article
C2 - 27430022
VL - 1
JO - JCI INSIGHT
JF - JCI INSIGHT
SN - 2379-3708
IS - 9
ER -