C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis.

Authors: Rufanova, VA  Lianos, E  Alexanian, A  Sorokina, E  Sharma, M  McGinty, A  Sorokin, A 
Citation: Rufanova VA, etal., Kidney Int. 2009 Jan;75(1):31-40. doi: 10.1038/ki.2008.448. Epub 2008 Sep 10.
Pubmed: (View Article at PubMed) PMID:18784646
DOI: Full-text: DOI:10.1038/ki.2008.448

The guanine nucleotide exchange factor C3G, along with the CrkII adaptor protein, mediates GTP activation of the small GTPase proteins Rap1 and R-Ras, facilitating their activation of downstream signaling pathways, which had been found to be important in the pathogenesis of glomerulonephritis. We found that expression of C3G protein was upregulated in glomerular epithelial cells in an experimental model of accelerated anti-GBM antibody-induced glomerulonephritis expression. To determine the consequence of its increased expression, we transfected C3G (using adenoviral constructs) into cultured glomerular epithelial cells and measured the activated forms (i.e., GTP-bound) forms of Rap1 and R-Ras. Activation of Rap1 was not affected by C3G; however, the basal level of GTP-bound R-Ras was decreased. Further, C3G over-expression enhanced the activation of R-Ras in response to endothelin. Overexpression of C3G also led to a significant reduction in glomerular epithelial cell spreading and decreased the cells' E-cadherin expression and augmented their migration. We found that C3G was overexpressed in accelerated anti-GBM antibody-induced glomerulonephritis and suggest that this modulates glomerular epithelial cell morphology and behavior.


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CRRD ID: 11534983
Created: 2016-09-15
Species: All species
Last Modified: 2016-09-15
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.