Dopamine responsiveness is regulated by targeted sorting of D2 receptors

S E Bartlett, Johan Enquist, F W Hopf, J H Lee, F Gladher, V Kharazia, M Waldhoer, W S Mailliard, R Armstrong, A Bonci, J L Whistler

Research output: Contribution to journalArticlepeer-review

130 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)11521-11526
JournalProceedings of the National Academy of Sciences
Volume102
Issue number32
DOIs
Publication statusPublished - 2005

Subject classification (UKÄ)

  • Pharmacology and Toxicology

Keywords

  • down-regulation
  • G protein-coupled receptor
  • trafficking
  • resensitization
  • degradation

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