Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Bartlett, Selena, Enquist, Johan, Hopf, F. Woodward, Lee, Josephine, Gladher, Fredrik, Kharazia, Viktor, Waldhoer, Maria, Mailliard, William, Armstrong, Randall, Bonci, Antonello, & Whistler, Jennifer (2005) Dopamine responsiveness is regulated by targeted sorting of D2 receptors. Proceedings of the National Academy of Sciences of the United States of America, 102(32), pp. 11521-11526.

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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.

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ID Code: 45102
Item Type: Journal Article
Refereed: Yes
Keywords: G protein-coupled receptor, trafficking, down-regulation, resensitization, degradation
DOI: 10.1073/pnas.0502418102
ISSN: 1091-6490
Deposited On: 24 Aug 2011 22:17
Last Modified: 29 Feb 2012 14:35

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