Insights into the regulation of 5-HT2A serotonin receptors by scaffolding proteins and kinases

Neuropharmacology. 2008 Nov;55(6):961-8. doi: 10.1016/j.neuropharm.2008.06.048. Epub 2008 Jul 2.


5-HT(2A) serotonin receptors are essential molecular targets for the actions of LSD-like hallucinogens and atypical antipsychotic drugs. 5-HT(2A) serotonin receptors also mediate a variety of physiological processes in peripheral and central nervous systems including platelet aggregation, smooth muscle contraction, and the modulation of mood and perception. Scaffolding proteins have emerged as important regulators of 5-HT(2A) receptors and our recent studies suggest multiple scaffolds exist for 5-HT(2A) receptors including PSD95, arrestin, and caveolin. In addition, a novel interaction has emerged between p90 ribosomal S6 kinase and 5-HT(2A) receptors which attenuates receptor signaling. This article reviews our recent studies and emphasizes the role of scaffolding proteins and kinases in the regulation of 5-HT(2A) trafficking, targeting and signaling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrestin / metabolism*
  • Caveolins / metabolism*
  • Endocytosis / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Models, Biological
  • Protein Transport / physiology
  • Receptor, Serotonin, 5-HT2A / physiology*
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism*


  • Arrestin
  • Caveolins
  • Intracellular Signaling Peptides and Proteins
  • Receptor, Serotonin, 5-HT2A
  • Ribosomal Protein S6 Kinases, 90-kDa