Regulated rapid round trips: Endocytotic cycling of the dopamine transporter shapes motor learning

The level of dopamine transporters (DATs) in the neuronal plasma membrane shapes learning and motor coordination in mice. Mechanisms underlying the regulated internalization of DAT and its return to the cell surface have been intensively studied in heterologous cells and in neuronal cell bodies. However, whether this cycling also happens in synaptic boutons, or axon terminals, thought to be the major functional site for DAT expression, was an open question that Kearney and colleagues recently addressed in the JBC. They showed that DAT cycling in the presynaptic specialization of dopaminergic neurons is subject to control by a cell-autonomous loop comprising dopamine autoreceptors and metabotropic glutamate receptors. These results should inform future studies in neural development and motor learning.