pH-dependent translocation of α-tocopherol transfer protein (α-TTP) between hepatic cytosol and late endosomes

Masakuni Horiguchi, Makoto Arita, Daisy E. Kaempf-Rotzoll, Masafumi Tsujimoto, Keizo Inoue, Hiroyuki Arai

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Abstract

Background: α-Tocopherol transfer protein (α-TTP), a member of the Sec14 protein family, plays an important role in transporting α-tocopherol, a major lipid-soluble anti-oxidant, in the cytosolic compartment of hepatocytes and is known as a product of the causative gene for familial isolated vitamin E deficiency. It has been shown that the secretion of hepatocyte α-tocopherol taken up with plasma lipoproteins is facilitated by α-TTP. To explore the mechanism of α-TTP mediated α-tocopherol secretion, we investigated drugs which may affect this secretion. Results: We found that, in a hepatocyte cell culture system, intracellular α-tocopherol transport is impaired by chloroquine, an agent known for its function of elevating the pH in acidic compartments. Under chloroquine treatment, the diffuse cytosolic distribution of α-TTP changes to a punctate pattern. Double-staining experiments with endocytosis markers revealed that α-TTP accumulates transiently on the cytoplasmic surface of late endosomal membranes. This phenomenon is specific for hepatoma cell lines or primarily cultured hepatocytes. Other members of the Sec14 family, such as cellular retinaldehyde-binding protein (CRALBP) and supernatant protein factor (SPF), do not show this accumulation. Furthermore, we elucidate that the obligatory amino acid sequence for this function is located between amino acids 21 and 50, upstream of the N-terminal end of the lipid-binding domain. Conclusion: We hypothesize that a fiver-specific target molecule for α-TTP exists on the late endosomal membrane surface. This transient binding may explain the mechanism of how α-tocopherol is transferred from late endosomes to cytosolic α-TTP.

Original languageEnglish
Pages (from-to)789-800
Number of pages12
JournalGenes to Cells
Volume8
Issue number10
DOIs
Publication statusPublished - 2003 Oct

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ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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