Rac1 activation in podocytes induces rapid foot process effacement and proteinuria

Haiyang Yu, Hani Suleiman, Alfred H.J. Kim, Jeffrey H. Miner, Adish Dani, Andrey S. Shaw, Shreeram Akilesh

Research output: Contribution to journalArticle

72 Scopus citations

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.

Original languageEnglish
Pages (from-to)4755-4764
Number of pages10
JournalMolecular and cellular biology
Volume33
Issue number23
DOIs
StatePublished - Dec 2013

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