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J Biol Chem. 2016 Aug 12;291(33):17028-39. doi: 10.1074/jbc.M116.734210. Epub 2016 Jun 15.

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

Author information

1
From the Departments of Nutrition.
2
the Department of Chemistry, Brock University, St. Catharines, Ontario L2S 3A1, Canada, and.
3
the Division of Nutritional Sciences, Cornell University, Ithaca, New York 14853.
4
Microbiology and Molecular Biology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
5
From the Departments of Nutrition, Pharmacology, and dxm178@case.edu.

Abstract

α-Tocopherol (vitamin E) is an essential nutrient for all vertebrates. From the eight naturally occurring members of the vitamin E family, α-tocopherol is the most biologically active species and is selectively retained in tissues. The hepatic α-tocopherol transfer protein (TTP) preferentially selects dietary α-tocopherol and facilitates its transport through the hepatocyte and its secretion to the circulation. In doing so, TTP regulates body-wide levels of α-tocopherol. The mechanisms by which TTP facilitates α-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 α-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 α-tocopherol, TTP- and α-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 α-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 α-tocopherol. These findings provide the basis for a proposed mechanistic model that describes TTP-facilitated trafficking of α-tocopherol through hepatocytes.

KEYWORDS:

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

PMID:
27307040
PMCID:
PMC5016108
DOI:
10.1074/jbc.M116.734210
[Indexed for MEDLINE]
Free PMC Article

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