Rac1 activation in podocytes induces rapid foot process effacement and proteinuria.

Abstract:

:The kidney's vital filtration function depends on the structural integrity of the glomerulus, the proximal portion of the nephron. Within the glomerulus, the architecturally complex podocyte forms the final cellular barrier to filtration. Injury to the podocyte results in a morphological change called foot process effacement, which is a ubiquitous feature of proteinuric diseases. The exact mechanism underlying foot process effacement is not known, but recently it has been proposed that this change might reflect activation of the Rac1 GTPase. To test this hypothesis, we generated a podocyte-specific, inducible transgenic mouse line that expressed constitutively active Rac1. When the Rac1 transgene was induced, we observed a rapid onset of proteinuria with focal foot process effacement. Using superresolution imaging, we verified that the induced transgene was expressed in damaged podocytes with altered foot process morphology. This work sheds new light on the complex balance of Rho GTPase signaling that is required for proper regulation of the podocyte cytoskeleton.

journal_name

Mol Cell Biol

authors

Yu H,Suleiman H,Kim AH,Miner JH,Dani A,Shaw AS,Akilesh S

doi

10.1128/MCB.00730-13

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

4755-64

issue

23

eissn

0270-7306

issn

1098-5549

pii

MCB.00730-13

journal_volume

33

pub_type

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