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Mol Biol Cell. 2017 Apr 15;28(8):1111-1122. doi: 10.1091/mbc.E16-07-0499. Epub 2017 Feb 16.

Role of STARD4 in sterol transport between the endocytic recycling compartment and the plasma membrane.

Author information

1
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065.
2
Weill Cornell Medical College, Rockefeller University, and Memorial Sloan-Kettering Cancer Center Tri-Institutional Chemical Biology Program, New York, NY 10065.
3
Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065 frmaxfie@med.cornell.edu.

Abstract

Cholesterol is an essential constituent of membranes in mammalian cells. The plasma membrane and the endocytic recycling compartment (ERC) are both highly enriched in cholesterol. The abundance and distribution of cholesterol among organelles are tightly controlled by a combination of mechanisms involving vesicular and nonvesicular sterol transport processes. Using the fluorescent cholesterol analogue dehydroergosterol, we examined sterol transport between the plasma membrane and the ERC using fluorescence recovery after photobleaching and a novel sterol efflux assay. We found that sterol transport between these organelles in a U2OS cell line has a t1/2 =12-15 min. Approximately 70% of sterol transport is ATP independent and therefore is nonvesicular. Increasing cellular cholesterol levels dramatically increases bidirectional transport rate constants, but decreases in cholesterol levels have only a modest effect. A soluble sterol transport protein, STARD4, accounts for ∼25% of total sterol transport and ∼33% of nonvesicular sterol transport between the plasma membrane and ERC. This study shows that nonvesicular sterol transport mechanisms and STARD4 in particular account for a large fraction of sterol transport between the plasma membrane and the ERC.

PMID:
28209730
PMCID:
PMC5391187
DOI:
10.1091/mbc.E16-07-0499
[Indexed for MEDLINE]
Free PMC Article

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