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J Cell Sci. 2016 Oct 1;129(19):3675-3684. Epub 2016 Aug 5.

Gα12 is required for renal cystogenesis induced by Pkd1 inactivation.

Author information

1
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
2
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Renal Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
3
Renal Division, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
4
Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA tqkong@gmail.com.

Abstract

Mutation of PKD1, encoding the protein polycystin-1 (PC1), is the main cause of autosomal dominant polycystic kidney disease (ADPKD). The signaling pathways downstream of PC1 in ADPKD are still not fully understood. Here, we provide genetic evidence for the necessity of Gα12 (encoded by Gna12, hereafter Gα12) for renal cystogenesis induced by Pkd1 knockout. There was no phenotype in mice with deletion of Gα12 (Gα12-/-). Polyinosine-polycytosine (pI:pC)-induced deletion of Pkd1 (Mx1Cre+Pkd1f/fGα12+/+) in 1-week-old mice resulted in multiple kidney cysts by 9 weeks, but the mice with double knockout of Pkd1 and Gα12 (Mx1Cre+Pkd1f/fGα12-/-) had no structural and functional abnormalities in the kidneys. These mice could survive more than one year without kidney abnormalities except multiple hepatic cysts in some mice, which indicates that the effect of Gα12 on cystogenesis is kidney specific. Furthermore, Pkd1 knockout promoted Gα12 activation, which subsequently decreased cell-matrix and cell-cell adhesion by affecting the function of focal adhesion and E-cadherin, respectively. Our results demonstrate that Gα12 is required for the development of kidney cysts induced by Pkd1 mutation in mouse ADPKD.

KEYWORDS:

Cadherin; G proteins; Polycystin-1; and Polycystic kidney diseases

PMID:
27505895
PMCID:
PMC5087651
DOI:
10.1242/jcs.190496
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

The authors declare no competing or financial interests.

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