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

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.

journal_name

Mol Biol Cell

authors

Iaea DB,Mao S,Lund FW,Maxfield FR

doi

10.1091/mbc.E16-07-0499

subject

Has Abstract

pub_date

2017-04-15 00:00:00

pages

1111-1122

issue

8

eissn

1059-1524

issn

1939-4586

pii

mbc.E16-07-0499

journal_volume

28

pub_type

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