Phosphatidylinositol (4,5)-bisphosphate modulates Nox5 localization via an N-terminal polybasic region.

ABSTRACT: Nox5, an EF-hand-containing reactive oxygen species (ROS)-generating NADPH oxidase, contains two conserved polybasic regions: one N-terminal (PBR-N), located between the fourth EF-hand and the first transmembrane region, and one C-terminal (PBR-C), between the first and second NADPH-binding subregions. Here, we show that phosphatidylinositol (4,5)-bisphosphate [PtdIns(4,5)P(2)], a major phosphoinositide in plasma membrane, binds to human Nox5 causing Nox5 to localize from internal membranes to the plasma membrane. Enzymatic modulation of PtdIns(4,5)P(2) levels in intact cells altered cell surface localization of Nox5 in parallel with extracellular ROS generation. Mutations in PBR-N prevented PtdIns(4,5)P(2)-dependent localization of Nox5 to the plasma membrane and decreased extracellular R

SUBMITTER: Kawahara T 

PROVIDER: S-EPMC2555958 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature