Vitamin E and Phosphoinositides Regulate the Intracellular Localization of the Hepatic ?-Tocopherol Transfer Protein.

ABSTRACT: ?-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of the vitamin E family, ?-tocopherol is the most biologically active species and is selectively retained in tissues. The hepatic ?-tocopherol transfer protein (TTP) preferentially selects dietary ?-tocopherol and facilitates its transport through the hepatocyte and its secretion to the circulation. In doing so, TTP regulates body-wide levels of ?-tocopherol. The mechanisms by which TTP facilitates ?-tocopherol trafficking in hepatocytes are poorly understood. We found that the intracellular localization of TTP in hepatocytes is dynamic and responds to the presence of ?-tocopherol. In the absence of the vitamin, TTP is localized to perinuclear vesicles that harbor CD71, transferrin, and Rab8, markers of the recycling endosomes. Upon treatment with ?-tocopherol, TTP- and ?-tocopherol-containing vesicles translocate to the plasma membrane, prior to secretion of the vitamin to the exterior of the cells. The change in TTP localization is specific to ?-tocopherol and is time- and dose-dependent. The aberrant intracellular localization patterns of lipid binding-defective TTP mutants highlight the importance of protein-lipid interaction in the transport of ?-tocopherol. These findings provide the basis for a proposed mechanistic model that describes TTP-facilitated trafficking of ?-tocopherol through hepatocytes.

SUBMITTER: Chung S 

PROVIDER: S-EPMC5016108 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature