Modulation of LAT1 (SLC7A5) transporter activity and stability by membrane cholesterol.
作者： David Dickens , George N. Chiduza , Gareth S. A. Wright , Munir Pirmohamed , Svetlana V. Antonyuk
DOI: 10.1038/SREP43580
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摘要: LAT1 (SLC7A5) is a transporter for both the uptake of large neutral amino acids and number pharmaceutical drugs. It expressed in numerous cell types including T-cells, cancer cells brain endothelial cells. However, mechanistic knowledge how it functions its interactions with lipids are unknown or limited due to inability obtaining stable purified protein sufficient quantities. Our data show that depleting cellular cholesterol reduced Vmax but not Km mediated model substrate into (L-DOPA). A soluble analogue was required purification chaperon CD98 (4F2hc,SLC3A2) this stabilised complex retained ability interact substrate. We propose interacts conserved regions have been shown bind cholesterol/CHS Drosophila melanogaster dopamine transporter. In conclusion, modulated by impacting on stability activity. This novel finding has implications other SLC7 family members additional eukaryotic transporters contain LeuT fold.
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