VACM‐1, a cul 5 Gene, Regulates Aquaporin‐1 Levels

Abstract

VACM‐1/cul 5 cDNA expression in Cos‐1 cells inhibits cell growth. The mechanism of this regulation involves MAPK phosphorylation, but the direct target of VACM‐1 activity is not known. After identifying VACM‐1 as a regulator of AQP1 protein and mRNA levels in vitro, we sought to elucidate effects of VACM‐1 expression on AQP1 in vivo in response to osmotic stress. In rats deprived of water for twenty‐four hours, VACM‐1 mRNA and protein levels were significantly higher in the heart ventricle but not the heart atrium when compared to the control group. Twenty‐four hour water deprivation also increased modification of VACM‐1 by the ubiquitin‐like protein Nedd8 in the heart ventricle and mesenteric arteries. Although water deprivation did not change mesenteric AQP1 levels significantly, AQP1 protein levels were inversely correlated with the ratio of VACM‐1 to the Nedd8 modified VACM‐1 protein. In summary, these results suggest that VACM‐1/cul 5 protein may regulate endothelial AQP1 concentration both in vivo and in vitro. This work was funded by the Arnold and Mabel Beckman Foundation.