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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.

SUBMITTER: Bartlett SE

PROVIDER: S-EPMC1183554 | biostudies-literature | 2005 Aug

REPOSITORIES: biostudies-literature

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Dopamine responsiveness is regulated by targeted sorting of D2 receptors.

Bartlett Selena E SE Enquist Johan J Hopf Frederic W FW Lee Josephine H JH Gladher Fredrik F Kharazia Viktor V Waldhoer Maria M Mailliard William S WS Armstrong Randall R Bonci Antonello A Whistler Jennifer L JL

Proceedings of the National Academy of Sciences of the United States of America 20050727 32

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 ...[more]

PMID: 16049099

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