Dopamine responsiveness is regulated by targeted sorting of D2 receptors

Research output: Contribution to journalArticle

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.

Details

Authors
  • 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • down-regulation, G protein-coupled receptor, trafficking, resensitization, degradation
Original languageEnglish
Pages (from-to)11521-11526
JournalProceedings of the National Academy of Sciences
Volume102
Issue number32
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes