Localization and expression profile of activator of G‐protein signaling proteins in the kidney (690.6)

Abstract

Activator of G‐protein signaling (AGS) are a family of accessory proteins that regulate heterotrimeric G‐protein function in a receptor‐independent mechanism. Recent studies in our lab have identified a crucial role for AGS3/GPSM1 in the recovery of the renal epithelial cells following acute kidney injury. Under normal conditions, AGS3/GPSM1 is exclusively expressed in the distal and collecting ducts. Following ischemia‐reperfusion injury, AGS3/GPSM1 is induced in the proximal tubules in the outer medulla, which is a highly sensitive site of injury due to ischemia. To determine whether other AGS proteins are expressed and may demonstrate biological activity during acute kidney injury, this study was designed to localize AGS proteins within the kidney using immunohistochemistry, and also determine the renal expression profile using quantitative RT‐PCR of all 13 known AGS proteins during quiescence and following an injury response. AGS1 was found to be predominantly localized to the proximal tubule in the renal cortex and outer medulla from mice, whereas AGS3, 5, and 8 were exclusively localized to the distal and collecting ducts in rat kidneys. In rat kidneys following ischemia‐reperfusion injury, AGS1 and AGS7 were both dramatically increased after 24 hours by 6‐7 fold, and slowly decreased towards normal (sham) levels at 72 and 168 hours after reperfusion. Messenger RNA levels of AGS4, 8, 9, 10, 11 and 12 were decreased by 40‐90% in the ischemia‐reperfusion injured kidneys compared to their sham (time‐control) kidneys at 24 hours, which tended to return towards normal (sham) levels by 168 hours after reperfusion. This study provides new information as to the site of synthesis of AGS protein, and could shed new light on their potential roles during normal and pathologic conditions in the kidney.Grant Funding Source: Supported by National Institutes of Health