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.
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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|Item Type:||Journal Article|
|Keywords:||G protein-coupled receptor, trafficking, down-regulation, resensitization, degradation|
|Deposited On:||24 Aug 2011 22:17|
|Last Modified:||29 Feb 2012 14:35|
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