Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol.

ABSTRACT: LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and a number of pharmaceutical drugs. It is expressed in numerous cell types including T-cells, cancer cells and brain endothelial cells. However, mechanistic knowledge of how it functions and its interactions with lipids are unknown or limited due to inability of obtaining stable purified protein in sufficient quantities. Our data show that depleting cellular cholesterol reduced the V_max but not the K_m of the LAT1 mediated uptake of a model substrate into cells (L-DOPA). A soluble cholesterol analogue was required for the stable purification of the LAT1 with its chaperon CD98 (4F2hc,SLC3A2) and that this stabilised complex retained the ability to interact with a substrate. We propose chol

SUBMITTER: Dickens D 

PROVIDER: S-EPMC5341093 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature