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

Item Type:Article
Title:Stimulation- and palmitoylation-dependent changes in oligomeric conformation of serotonin 5-HT1A receptors
Creators Name:Kobe, F. and Renner, U. and Woehler, A. and Wlodarczyk, J. and Papusheva, E. and Bao, G. and Zeug, A. and Richter, D. and Neher, E. and Ponimaskin, E.
Abstract: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.
Keywords:Oligomerization, Serotonin, G-Protein Coupled Receptors, Palmitoylation, Foerster Resonance Energy Transfer, Animals, Mice
Source:Biochimica et Biophysica Acta - Molecular Cell Research
ISSN:0167-4889
Publisher:Elsevier Science BV (The Netherlands)
Volume:1783
Number:8
Page Range:1503-1516
Date:August 2008
Official Publication:https://doi.org/10.1016/j.bbamcr.2008.02.021
PubMed:View item in PubMed

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