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

作者：Chung Stacey; Ghelfi Mikel; Atkinson Jeffrey; Parker Robert; Qian Jinghui; Carlin Cathleen; Manor Danny^*

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 2016, 291(33): 17028-17039.

DOI：10.1074/jbc.M116.734210

• lipid trafficking
• lipid transport
• phosphatidylinositol signaling
• phosphoinositide
• vitamin E
• tocopherol
• tocopherol transfer protein

-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.

• 出版日期2016-8