Dopamine Responsiveness is Regulated by Targeted Sorting of D2 Receptors

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2005 Jul 29

PMID 16049099

Citations 90

Authors

Selena E Bartlett

Johan Enquist

Frederic W Hopf

Josephine H Lee

Fredrik Gladher

Viktor Kharazia

Maria Waldhoer

William S Mailliard

Randall Armstrong

Antonello Bonci

Jennifer L Whistler

Affiliations

Soon will be listed here.

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.

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