Endosomal Recycling of the Na+/H+Exchanger NHE3 Isoform Is Regulated by the Phosphatidylinositol 3-Kinase Pathway

摘要: The NHE3 isoform of the Na+/H+ exchanger localizes to both plasmalemmal and endosomal compartments in polarized epithelial transfected Chinese hamster ovary (AP-1) cells. It is unclear how distribution between these regulated. In this study, we examined potential involvement phosphatidylinositol 3′-kinase (PI3-K) regulating activity NHE3, as lipid kinase has been implicated modulating vesicular traffic recycling pathway. Wortmannin LY294002, potent inhibitors PI3-K, markedly inhibited NHE3-mediated H+ extrusion across plasma membrane a concentration- time-dependent manner. subcellular antiporters was monitored by transfecting epitope-tagged into AP-1 parallel with inhibition transport, PI3-K antagonists induced pronounced loss from cell surface its accumulation an intracellular compartment, assessed immunofluorescence microscopy enzyme-linked immunosorbent assays. Further analysis using cells bearing external epitope tag revealed that redistribution reflected primarily decrease rate surface. wortmannin-induced were prevented when incubated at 4 °C, consistent known temperature dependence endocytic process. These observations demonstrate controlled dynamic events are modulated PI3-K.