Localization and expression profile of Group I and II Activators of G-protein Signaling in the kidney

Abstract

Activators of G-protein Signaling (AGS) are a family of accessory proteins that were discovered as modulators of heterotrimeric G-protein subunits. The primary aim of the present study was to localize Group I and II AGS proteins and determine the renal expression profile using immunohistochemistry and quantitative RT-PCR, respectively, during normal and injured states of the kidney. Group I AGS1 was found to be predominantly localized to the proximal tubule, Group II AGS3 and AGS5 were exclusively localized to the distal tubular segments, and Group II AGS6 was ubiquitously expressed in every nephron segment of the rodent kidney. In rat kidneys following ischemia-reperfusion injury (IRI), Group I AGS1 mRNA was dramatically increased after 24 hours by 5-fold (P<0.05), whereas Group II AGS3 and AGS4 mRNA was significantly decreased at the same time point (P<0.05). No significant change in the transcript levels were detected at other time points for any of the AGS genes between control and IRI groups. In polycystic diseased kidneys, mRNA levels for AGS3, AGS4 and AGS6 was significantly increased (P<0.05) by 75–80% in PCK rat kidneys. The identification of Group I and II AGS mRNA and protein in the kidney may provide insight into the potential mechanism of action during normal and varying states of renal disease or injury.

Activators of G Protein Signaling in the Kidney

“…This was consistent with the Trip13 protein localization found only in the principal cells of the collecting ducts in the normal rat kidney (Lenarcyzk et al, 2014a). The site of expression in the nephron may implicate AGS7/Trip13 as a potential regulator of Na 1 , water, or urea reabsorption, but the biologic importance of AGS7/Trip13 during normal and pathologic conditions in the kidney needs further investigation.…”

“…The expression profile for AGS6/RGS12 in the kidney may be species or isoform dependent, since multiple RGS12 mRNA isoforms were expressed in the human kidneys (Snow et al, 1998), but not in mouse kidneys (Yang and Li, 2007). At the protein level, however, we have observed low uniform staining throughout the rat nephron and the endothelial cells of the blood vessels in the renal cortex (Lenarczyk et al, 2014b).…”

“…In the normal rat kidneys, AGS5/LGN was detected in the distal tubules, including thick ascending limb and collecting ducts (Lenarczyk et al, 2014a,b). Unlike AGS3/GPSM1, there was no observable change in the AGS5/LGN protein levels or localization pattern after acute kidney injury (Regner et al, 2011;Lenarczyk et al, 2014b) or in genetically mutant cystic kidneys (Nadella et al, 2010).…”

“…During hypertrophy, AGS3/GPSM1 protein expression was not induced (Lenarczyk et al, 2014b). Moreover, unilateral nephrectomy in the Gpsm1-deficient mice did not affect the ability of the remaining kidney to increase its size compared with wild-type mice (Lenarczyk et al, 2014b).…”

“…However, AGS3/GPSM1 does not appear to play a role during compensatory hypertrophy, which is an alternate mechanism to produce increased cell size (Lenarczyk et al, 2014b). During hypertrophy, AGS3/GPSM1 protein expression was not induced (Lenarczyk et al, 2014b).…”