Dopamine transporter phosphorylation site threonine 53 regulates substrate reuptake and amphetamine-stimulated efflux

Low levels of extraneuronal dopamine are controlled primarily by the action of the dopamine transporter, and specific phosphorylation sites in native DAT under basal condition with associated functional properties have not been ascertained so far.

Abstract

Background In the central nervous system, levels of extraneuronal dopamine are controlled primarily by the action of the dopamine transporter (DAT). Multiple signaling pathways regulate transport activity, substrate efflux, and other DAT functions through currently unknown mechanisms but presumably by oligomerization, protein-protein interactions and post-translational modification, such as phosphorylation. DAT is phosphorylated by protein kinase C within a serine cluster at the distal end of the cytoplasmic N-terminus, while recent work in model cells revealed proline-directed phosphorylation of rat DAT at membrane proximal residue Thr53. However, specific phosphorylation sites in native DAT under basal condition with associated functional properties have not been ascertained so far.