Document Detail

Arhgap24 inactivates Rac1 in mouse podocytes, and a mutant form is associated with familial focal segmental glomerulosclerosis.
MedLine Citation:
PMID:  21911940     Owner:  NLM     Status:  MEDLINE    
The specialized epithelial cell of the kidney, the podocyte, has a complex actin-based 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.
Shreeram Akilesh; Hani Suleiman; Haiyang Yu; M Christine Stander; Peter Lavin; Rasheed Gbadegesin; Corinne Antignac; Martin Pollak; Jeffrey B Kopp; Michelle P Winn; Andrey S Shaw
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-09-12
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  121     ISSN:  1558-8238     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-03     Completed Date:  2011-11-21     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4127-37     Citation Subset:  AIM; IM    
Department of Pathology, Barnes-Jewish Hospital, St. Louis, Missouri 63110, USA.
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MeSH Terms
Amino Acid Sequence
Cell Differentiation
Cell Membrane / pathology
Cell Shape
GTPase-Activating Proteins / antagonists & inhibitors,  genetics*,  physiology*
Gene Knockdown Techniques
Glomerulosclerosis, Focal Segmental / genetics*,  pathology,  physiopathology*
Molecular Sequence Data
Mutant Proteins / genetics,  physiology
Neuropeptides / antagonists & inhibitors*,  physiology
Podocytes / pathology,  physiology*
Sequence Homology, Amino Acid
rac GTP-Binding Proteins / antagonists & inhibitors*,  physiology
Grant Support
DK079333/DK/NIDDK NIH HHS; R01 DK058366/DK/NIDDK NIH HHS; R01DK058366/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute
Reg. No./Substance:
0/ARHGAP24 protein, human; 0/ARHGAP24 protein, mouse; 0/GTPase-Activating Proteins; 0/Mutant Proteins; 0/Neuropeptides; 0/Rac1 protein, mouse; EC GTP-Binding Proteins

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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