Endothelial Caveolar Hub Regulation of Adenosine Triphosphate–Induced Endothelial Nitric Oxide Synthase Subcellular Partitioning and Domain-Specific (original) (raw)

2016

Abstract

Abstract—ATP leads to endothelial NO synthase (eNOS)/NO-mediated vasodilation, a process hypothesized to depend on the endothelial caveolar eNOS partitioning and subcellular domain-specific multisite phosphorylation state. We demonstrate herein that, in both the absence and presence of ATP, the uterine artery endothelial caveolae contain specific protein machinery related to subcellular partitioning and act as specific focal “hubs ” for NO- and ATP-related proteins. ATP-induced eNOS regulation showed a complex set of multisite posttranslational phosphorylation events that were closely associated with the enzyme’s partitioning between caveolar and noncaveolar endothelial subcellular domains. The comprehensive model that we present demonstrates that ATP repartitioned eNOS between the caveolar and noncaveolar subcellular domains; specifically, the stimulatory PSer635eNOS was substantially higher in the caveolar pool with subcellular domain-independent increased levels on ATP treatment....

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