title: Dopamine responsiveness is regulated by targeted sorting of D2 receptors.
abstract: Aberrant dopaminergic signaling is a critical determinant in multiple psychiatric disorders, and in many disease states, dopamine receptor number is altered. Here we identify a molecular mechanism that selectively targets D2 receptors for degradation after their activation by dopamine. The degradative fate of D2 receptors is determined by an interaction with G protein coupled receptor-associated sorting protein (GASP). As a consequence of this GASP interaction, D2 responses in rat brain fail to resensitize after agonist treatment. Disruption of the D2-GASP interaction facilitates recovery of D2 responses, suggesting that modulation of the D2-GASP interaction is important for the functional down-regulation of D2 receptors.
authors.affiliation: Ernest Gallo Clinic and Research Center, University of California, San Francisco, CA 94608, USA.
authors.forename: Selena E
authors.initials: SE
authors.lastname: Bartlett
authors.forename: Johan
authors.initials: J
authors.lastname: Enquist
authors.forename: Frederic W
authors.initials: FW
authors.lastname: Hopf
authors.forename: Josephine H
authors.initials: JH
authors.lastname: Lee
authors.forename: Fredrik
authors.initials: F
authors.lastname: Gladher
authors.forename: Viktor
authors.initials: V
authors.lastname: Kharazia
authors.forename: Maria
authors.initials: M
authors.lastname: Waldhoer
authors.forename: William S
authors.initials: WS
authors.lastname: Mailliard
authors.forename: Randall
authors.initials: R
authors.lastname: Armstrong
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Whistler
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D004298:Dopamine / Q000378:metabolism*; D015536:Down-Regulation; D004594:Electrophysiology; D005982:Glutathione Transferase; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: C463459:GPRASP1 protein, human; D017448:Receptors, Dopamine D2; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; D005982:Glutathione Transferase; D004298:Dopamine