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Dopamine transporter cell surface localization facilitated by a direct interaction with the dopamine D2 receptor
Author(s) -
Lee Frank JS,
Pei Lin,
Moszczynska Anna,
Vukusic Brian,
Fletcher Paul J,
Liu Fang
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601656
Subject(s) - dopamine plasma membrane transport proteins , dopamine transporter , dopamine , reuptake , neurotransmitter , dopaminergic , biology , dopamine receptor d2 , neurotransmitter receptor , dopamine receptor , d1 like receptor , neurotransmitter transporter , d2 like receptor , dopamine receptor d3 , synaptic cleft , receptor , neuroscience , biochemistry , serotonin
Altered synaptic dopamine levels have been implicated in several neurological/neuropsychiatric disorders, including drug addiction and schizophrenia. However, it is unclear what precipitates these changes in synaptic dopamine levels. One of the key presynaptic components involved in regulating dopaminergic tone is the dopamine transporter (DAT). Here, we report that the DAT is also regulated by the dopamine D2 receptor through a direct protein–protein interaction involving the DAT amino‐terminus and the third intracellular loop of the D2 receptor. This physical coupling facilitates the recruitment of intracellular DAT to the plasma membrane and leads to enhanced dopamine reuptake. Moreover, mice injected with peptides that disrupt D2–DAT interaction exhibit decreased synaptosomal dopamine uptake and significantly increased locomotor activity, reminiscent of DAT knockout mice. Our data highlight a novel mechanism through which neurotransmitter receptors can functionally modulate neurotransmitter transporters, an interaction that can affect the synaptic neurotransmitter levels in the brain.