C3G overexpression in glomerular epithelial cells during anti-GBM-induced glomerulonephritis.
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.
Rufanova
Victoriya A
VA
Division of Nephrology and Kidney Disease Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Lianos
Elias
E
Alexanian
Anna
A
Sorokina
Elena
E
Sharma
Mukut
M
McGinty
Ann
A
Sorokin
Andrey
A
D000818:Animals; D001323:Autoantibodies / Q000009:adverse effects*; D015820:Cadherins / Q000235:genetics; D002448:Cell Adhesion; D002465:Cell Movement; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D005921:Glomerulonephritis / Q000139:chemically induced / Q000378:metabolism*; D020735:Guanine Nucleotide-Releasing Factor 2 / Q000235:genetics*; D007678:Kidney Glomerulus / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D001323:Autoantibodies; D015820:Cadherins; D020735:Guanine Nucleotide-Releasing Factor 2; C051951:antiglomerular basement membrane antibody
EMBO J. 2001 Jul 2;20(13):3333-41
11432821
J Hum Genet. 2004;49(6):290-295
15138850
J Biochem. 2003 Oct;134(4):479-84
14607972
Exp Biol Med (Maywood). 2006 Jun;231(6):1128-31
16741062
J Biol Chem. 2000 Jun 9;275(23):17596-604
10747877
Am J Physiol Renal Physiol. 2006 Mar;290(3):F710-9
16189286
J Thorac Cardiovasc Surg. 2004 Mar;127(3):746-54
15001903
J Cell Biol. 1999 May 31;145(5):1077-88
10352023
J Clin Invest. 1997 Aug 1;100(3):582-8
9239405
EMBO J. 1997 Nov 3;16(21):6439-51
9351826
J Am Soc Nephrol. 1992 Nov;3(5):1131-8
1336407
Kidney Int. 2005 Sep;68(3):1109-19
16105041
J Cell Biochem. 2006 May 15;98(2):451-68
16440301
Cell. 1997 Feb 21;88(4):521-30
9038343
Nephrol Dial Transplant. 1999 Dec;14(12):2860-72
10570089
Mol Biol Cell. 1999 Jun;10(6):1799-809
10359597
J Cell Sci. 2007 Jan 1;120(Pt 1):17-22
17182900
Carcinogenesis. 2003 Mar;24(3):573-82
12663520
J Pathol. 1996 Aug;179(4):414-20
8869290
Am J Kidney Dis. 1997 Jan;29(1):2-26
9002526
Biochem Soc Trans. 2003 Feb;31(Pt 1):83-6
12546659
Histopathology. 2003 Aug;43(2):173-9
12877733
Biochem Soc Trans. 2005 Dec;33(Pt 6):1265-8
16246094
Development. 2003 Jan;130(2):355-67
12466202
Mol Cell Biol. 2004 Aug;24(15):6690-700
15254236
J Am Soc Nephrol. 2008 Mar;19(3):495-502
18199804
Annu Rev Physiol. 1993;55:249-65
8466176
Int J Gynecol Cancer. 2006 Mar-Apr;16(2):763-71
16681758
Mol Cell Biol. 2001 Nov;21(21):7429-41
11585923
Kidney Int. 1978 Jul;14(1):21-30
682422
Nephron Clin Pract. 2007;106(2):c61-6
17570931
Biochem J. 2005 Jul 15;389(Pt 2):465-9
15725075
Kidney Int Suppl. 1993 Jan;39:S47-54
8468926
J Nephrol. 1999 Sep-Oct;12(5):297-307
10630692
FASEB J. 2006 May;20(7):976-8
16585060
Kidney Int. 2005 Feb;67(2):404-19
15673288
J Cell Sci. 2006 Apr 1;119(Pt 7):1307-19
16537651
EMBO J. 2006 Aug 9;25(15):3652-63
16858399
J Immunol. 1998 Nov 15;161(10):5755-61
9820557
Nature. 1998 Apr 9;392(6676):622-6
9560161
Am J Clin Pathol. 1972 Aug;58(2):135-9
5047603
J Am Soc Nephrol. 2005 Aug;16(8):2257-62
15987751
Kidney Int. 1996 Sep;50(3):962-72
8872972
J Tongji Med Univ. 1998;18(2):122-5
10806841
J Lab Clin Med. 2001 Jul;138(1):40-9
11433227
Mol Biol Cell. 2007 May;18(5):1850-60
17344481
Nephrol Dial Transplant. 2003 Aug;18 Suppl 6:vi8-13
12953035
Traffic. 2004 Jan;5(1):37-44
14675423
Mol Biol Cell. 2005 May;16(5):2458-69
15772154
J Cell Sci. 2006 Apr 1;119(Pt 7):1244-54
16522685
Oncogene. 2004 Jun 17;23(28):4885-93
15077165
Exp Cell Res. 2006 Apr 1;312(6):938-48
16443220