Neurotransmitter transporter trafficking: endocytosis, recycling, and regulation

Abstract

Sodium- and chloride-dependent transporters in the SLC6 gene family are key regulators of extracellular neurotransmitter levels and are required for normal neurotransmission. Copious evidence supports the premise that membrane trafficking dynamically modulates transporter surface expression in response to psychostimulant exposure, receptor activation, and neuronal activity. Recent work from our group and others demonstrates that many SLC6 transporters not only traffic in response to exogenous stimuli, but also constitutively traffic, with exogenous signaling modulating intrinsic transporter trafficking kinetics. This review focuses on what is currently understood about constitutive and regulated transporter trafficking, and poses a model wherein endocytic trafficking dynamically primes transporters for multi-faceted regulatory events.