Stimulation- and palmitoylation-dependent changes in oligomeric conformation of serotonin 5-HT1A receptors

Biochim Biophys Acta. 2008 Aug;1783(8):1503-16. doi: 10.1016/j.bbamcr.2008.02.021. Epub 2008 Mar 12.


In the present study we analyzed the oligomerization state of the serotonin 5-HT1A receptor and studied oligomerization dynamics in living cells. We also investigated the role of receptor palmitoylation in this process. Biochemical analysis performed in neuroblastoma N1E-115 cells demonstrated that both palmitoylated and non-palmitoylated 5-HT1A receptors form homo-oligomers and that the prevalent receptor species at the plasma membrane are dimers. A combination of an acceptor-photobleaching FRET approach with fluorescence lifetime measurements verified the interaction of CFP- and YFP-labeled wild-type as well as acylation-deficient 5-HT1A receptors at the plasma membrane of living cells. Using a novel FRET technique based on the spectral analysis we also confirmed the specific nature of receptor oligomerization. The analysis of oligomerization dynamics revealed that apparent FRET efficiency measured for wild-type oligomers significantly decreased in response to agonist stimulation, and our combined results suggest that this decrease was mediated by accumulation of FRET-negative complexes rather than by dissociation of oligomers to monomers. In contrast, the agonist-mediated decrease of FRET signal was completely abolished in oligomers composed by non-palmitoylated receptor mutants, demonstrating the importance of palmitoylation in modulation of the structure of oligomers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Dimerization
  • Fluorescence Resonance Energy Transfer
  • Lipoylation
  • Membrane Microdomains / chemistry
  • Mice
  • Photobleaching
  • Protein Conformation
  • Receptor, Serotonin, 5-HT1A / chemistry*
  • Receptor, Serotonin, 5-HT1A / metabolism
  • Serotonin 5-HT1 Receptor Agonists
  • Spectrometry, Fluorescence


  • Serotonin 5-HT1 Receptor Agonists
  • Receptor, Serotonin, 5-HT1A