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Résumé : Molecular biology of DAT and regulation of expression The DAT gene cloned from a rat brain expression library codes for 620 amino acids, with a sequence predicting 12 transmembrane domains (Giros et al . 1991). Its expression in various cell lines confers vulnerability to the toxin MPP+ (Pifl, Giros, & Caron 1993), in addition to conferring the ability to transport dopamine. The uptake of dopamine in striatal slices and synaptosomes has a saturable component with high affinity, and apparently also a high-capacity, low-affinity site (Mireylees, Brammer, & Buckley 1986). It is the saturable component that is characterized by sensitivity to cocaine and related compounds. Thus, the potency of many drugs displacing [ 3 H]cocaine from striatal membranes is highly correlated with the inhibition of [ 3 H]dopamine uptake in slices or synaptosome preparations (Madras et al . 1989). The intracellular domain of DAT presents several potential sites for phosphorylation by protein kinases C and A (Giros et al . 1992). Treatment with phorbol esters, which activate PKC directly, reduced the maximal velocity of [ 3 H]dopamine uptake by synaptosomes from rat striatum (Copeland et al . 1996), and also reduced the velocity of dopamine uptake in frog oocytes expressing human DAT (Zhu et al . 1997). This latter reduction in velocity was associated with reduced [ 3 H]mazindol binding to intact cells, without any concomitant change in the ligand binding to homogenates, which indicates that the treatment altered the association of functional transporters with the plasma membrane.