Clearance of synaptically released dopamine is regulated by the plasmalemmal dopamine
transporter (DAT), an integral membrane protein that resides within a complex lipid milieu.
Here we demonstrate that cholesterol, a major component of the lipid bilayer, can modulate
the conformation of DAT and alter cocaine binding to DAT. In striatal synaptosomes and
transfected cells, DAT was in cholesterol-rich membrane fractions after mild detergent
extraction. After increasing the membrane cholesterol content by treatment of water-soluble …