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Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomeruosclerosis
- Source :
- Journal of Clinical Investigation. October 1, 2011, Vol. 121 Issue 10, p4127, 11 p.
- Publication Year :
- 2011
-
Abstract
- The specialized epithelial cell of the kidney, the podocyte, has a complex actinbased cytoskeleton. Dynamic regulation of this cytoskeleton is required for efficient barrier function of the kidney. Podocytes are a useful cell type to study the control of the actin cytoskeleton in vivo, because disruption of components of the cytoskeleton results in podocyte damage, cell loss, and a prototypic injury response called focal segmental glomerulosclerosis (FSGS). Searching for actin regulatory proteins that are expressed in podocytes, we identified a RhoA-activated Rac1 GTPase-activating protein (Rac1-GAP), Arhgap24, that was upregulated in podocytes as they differentiated, both in vitro and in vivo. Increased levels of active Rac1 and Cdc42 were measured in Arhgap24 knockdown experiments, which influenced podocyte cell shape and membrane dynamics. Consistent with a role for Arhgap24 in normal podocyte functioning in vivo, sequencing of the ARHGAP24 gene in patients with FSGS identified a mutation that impaired its Rac1-GAP activity and was associated with disease in a family with FSGS. Thus, Arhgap24 contributes to the careful balancing of RhoA and Rac1 signaling in podocytes, the disruption of which may lead to kidney disease.<br />Introduction The kidneys filter plasma and reabsorb solutes and nutrients to maintain the appropriate extracellular environment. The proximal component of the nephron, the glomerulus, is the primary filtration barrier that [...]
Details
- Language :
- English
- ISSN :
- 00219738
- Volume :
- 121
- Issue :
- 10
- Database :
- Gale General OneFile
- Journal :
- Journal of Clinical Investigation
- Publication Type :
- Academic Journal
- Accession number :
- edsgcl.269437979
- Full Text :
- https://doi.org/10.1172/JCI46458