The plasma membrane dopamine transporter (DAT) and the vesicular monoamine
transporter (VMAT2) are essential for normal dopamine neurotransmission. DA
T terminates the actions of dopamine by rapidly removing dopamine from the
synapse, whereas VMAT2 loads cytoplasmic dopamine into vesicles for storage
and subsequent release. Recent data suggest that perturbation of the tight
ly regulated balance between these two transporters predisposes the neurone
to damage by a variety of insults. Most notable is the selective degenerat
ion of DAT- and VMAT2-expressing dopamine nerve terminals in the striatum t
hought to underlie Parkinson's disease. DAT and VMAT2 expression can predic
t the selective vulnerability of neuronal populations, which suggests that
therapeutic strategies aimed at altering DAT and VMAT2 function could have
significant benefits in a variety of disorders.