The ups and downs of neurotransmitter transporters

Plasma membrane neurotransmitter transporters are a family of integral membrane proteins, found on both neurons and glia, that have the capacity to influence neuronal signaling through a number of mechanisms including transmitter reuptake and ionic flux. Clinically, these proteins are of interest because their dysfunction is associated with several neurological and psychiatric disorders, and because they are the targets of many drugs of abuse and therapy. In this review, the authors focus on one of the more recent, fascinating discoveries about neurotransmitter transporters; namely, that transporter function is regulated by altering the number of transporters on the cell surface. These data suggest that transporter expression is in continual flux and that transporters respond to their environment in an effort to maintain baseline transmitter levels in the brain, The authors examine the mechanisms underlying changes in transporter number, discuss clinical disorders that are correlated with transporter expression, and suggest that controlling transporter redistribution may be a future therapeutic strategy for disorders related to abnormal transmitter levels.