Journal
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
Volume 91, Issue 10, Pages 773-782Publisher
CANADIAN SCIENCE PUBLISHING, NRC RESEARCH PRESS
DOI: 10.1139/cjpp-2013-0135
Keywords
Rho-GTPase; podocyte; proteinuria; cytoskeleton; nephrotic syndrome; GTPase-activating protein; guanine nucleotide exchange factor
Categories
Funding
- Canadian Institute of Health [MOP-53335, MOP-126180]
- Kidney Foundation of Canada
- Fonds de la recherche en sante du Quebec
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Podocytes play a critical role in maintaining glomerular permselectivity. It has been long recognized that their intricate actin-based structures are tightly associated with their normal function; however, the precise mechanisms by which podocytes form and maintain their complex structure had been poorly understood until the intensive investigations on podocyte biology began in 1998, triggered by the breakthrough discovery of nephrin. This review summarizes the recent discoveries of the molecular mechanisms by which the actin cytoskeleton is regulated in podocytes. A particular focus will be on the role of the Rho-family of small GTPases, represented by RhoA, Rac1, and Cdc42. Rho-GTPases are known for their versatile cellular functions, most importantly for the actin regulatory roles. We will also discuss the potential roles of the 3 groups of proteins known to regulate Rho-GTPases, namely GTPase-activating proteins, guanine nucleotide exchange factors, and guanine nucleotide dissociation inhibitors.
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