Dopamine responsiveness is regulated by targeted sorting of D2 receptors

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 Whistler

Research output: Contribution to journalArticle

121 Scopus citations

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 (US)
Pages (from-to)11521-11526
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number32
DOIs
StatePublished - Aug 9 2005
Externally publishedYes

Keywords

  • Degradation
  • Down-regulation
  • G protein-coupled receptor
  • Resensitization
  • Trafficking

ASJC Scopus subject areas

  • General

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    Bartlett, S. E., Enquist, J., Hopf, F. W., Lee, J. H., Gladher, F., Kharazia, V., Waldhoer, M., Mailliard, W. S., Armstrong, R., Bonci, A., & Whistler, J. (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), 11521-11526. https://doi.org/10.1073/pnas.0502418102