Table 1.

Accessory proteins for heterotrimeric G-proteins in the kidney.

Functional role	Accessory protein	G-protein subunit	Function	References
I. NORMAL PHYSIOLOGY
Receptor desensitization	GRK2/3	Gαq/11, Gβγ	Promotes redistribution to plasma membrane to inactivate GPCR signaling	Kamal et al., 2012; Sato et al., 2015
Cytoskeleton	Tubulin	Gαq, Gαi1, Gs	Gα-GTP promotes microtubule	Roychowdhury and Rasenick, 1994; Yan et al., 1996; Roychowdhury et al., 1999; Schappi et al., 2014
		Gβγ	Disassembly; Gβγ promotes microtubule polymerization
	Radixin	Gα13-GTP	Promotes conformational change to bind F-actin	Vaiskunaite et al., 2000
Second messenger system	RGS2	Gαs, Gαq	Partially inhibits water reabsorption by direct interaction between RGS2 with Gαs and adenylyl cyclase isoforms at the plasma membrane	Roy et al., 2003, 2006; Zuber et al., 2007
Ion transporters	AGS11/TFE3	Gα16	Regulates Npt2 expression	Miyamoto and Itho, 2001
	EBP50/NHERF1	Gαq	Gαq inhibits PLC-β1 signaling by binding to the same PDZ domains as PLC; dependency on G-protein binding to alter sodium and phosphate transport remains to be determined	Rochdi et al., 2002; Morales et al., 2004
Glomerular function	HSP90	Gα12, Gβγ	Regulate GFR through NO-dependent mechanism; role of G-proteins remains to be determined	Inanobe et al., 1994; Vaiskunaite et al., 2001; Ramirez et al., 2008
II. PATHOPHYSIOLOGY/KIDNEY DISEASE
Cystic kidney disease	RGS7	Gβ5	Interacts with C-terminal tail of PC-1; function unknown	Kim et al., 1999
	AGS3/GPSM1	Gαi/o	Attenuates cystic disease progression; activates heteromeric PC1/PC2 ion channel	Kwon et al., 2012; Nadella et al., 2010
	AGS5/LGN	Gαi/o	Loss of AGS5/LGN promotes abnormal cyst formation in MDCK cells	Zheng et al., 2010; Xiao et al., 2012
	AGS11/TFE3	Gα16	Associated with appearance of cysts in BHD; mechanism not known	Luijten et al., 2013
	HSP90	Gα12, Gβγ	Accelerates cystic disease; role of G-proteins not known	Seeger-Nukpezah et al., 2013
Acute kidney injury	RGS4	Gαi	Lack of RGS4 exacerbates the reduction in total blood flow after IRI; RGS4 competes for activated Gαq by ANGII to prevent secretion of RANTES	Siedlecki et al., 2011; Pang et al., 2015
	AGS1/Dexras1/RasD1		No known function	Rusai et al., 2013; Zhang et al., 2013
	AGS3/GPSM1	Gαi/o	Promotes tubular epithelial cell repair following IRI	Regner et al., 2011; Lenarczyk et al., 2015
	RACK1	Gβγ	Induction of proximal tubular RACK1 expression following IRI; functional role is not known	Padanilam and Hammerman, 1997
	HSP90	Gα12	HSP90 induction in proximal tubules after IRI; blockade of HSP90 activity reduces epithelial cells damage after IRI, but due to compensatory induction of other HSPs; over-expression of HSP90 restores coupling with eNOS after IRI to limit the extent of epithelial cell damage after IRI; role of G-protein interaction remains to be determined	Vaiskunaite et al., 2001
Glomerular injury/disease	RGS2	Gαq	RGS2 negatively regulates urotensin II-dependent calcium increase and contraction	Adebiyi, 2014
	GIV/Girdin	Gαi/o	Protects glomerulus from injury by activating PI3K/Akt pathway	Wang et al., 2015
	Rap1GAP	Gαi/o	Increased expression in podocytes from injury glomeruli promoted cellular detachment by inhibition activation of β1 integrin	Potla et al., 2014
Renal cancer	AGS11/TFE3	Gα16	Associated with nuclear localization of hybrid TFE3-fusion proteins in translocation renal cell carcinoma	Meloni et al., 1993; Weterman et al., 1996a,b, 2000, 2001; Kuiper et al., 2003; Mathur and Samuels, 2007
	Rap1GAP	Gαi/o	Loss of Rap1GAP promotes abnormal cell migration and invasion	Kim et al., 2012
	RGS5	Gαi/o	Selectively expressed in the blood vessel in renal cell carcinoma; may promote angiogenesis	Furuya et al., 2004
Fibrosis	RGS2	Gαq	Slows onset of renal fibrosis by blocking the AT1R activated pro-fibrogenic and inflammatory systems	Jang et al., 2014
Vascular hyperactivity and hypertension	RGS2	Gαq	Loss of renal RGS2 produces mild hypertension	Gurley et al., 2010
	RACK1	Gβγ	Hyperactive PLC/PKC increases vascular cell proliferation in in hypertensive rats in vitro	Cheng et al., 2011