Phosphorylation and regulation of psychostimulant-sensitive neurotransmitter transporters

The neuronal transporters for the monoamines dopamine, serotonin, and norepinephrine are plasma membrane proteins that serve vital functions in the reuptake and control of synaptic neurotransmitter levels. They are also targets for abused and therapeutic drugs and play pivotal roles in neurological disorders such as depression, schizophrenia, and Parkinson's disease. There is increasing evidence that some activities of these carriers are subject to acute control by treatments that affect phosphorylation pathways, but the molecular basis for this is not understood. Recent work suggests that these regulatory processes may involve phosphorylation of the transporters by protein kinase C and other kinases, and may occur by affecting intrinsic transport activity or by controlling transporter cell surface expression. Phosphorylation-mediated regulation of monoamine transporters provides the potential for acute presynaptic control of neurotransmitter levels during normal neurophysiologic events, and dysregulation of these processes may lead to inappropriate transmitter clearance that contributes to the etiology of neurological disorders.