TY - JOUR T1 - Localization of the Mouse 5-Hydroxytryptamine<sub>1A</sub> Receptor in Lipid Microdomains Depends on Its Palmitoylation and Is Involved in Receptor-Mediated Signaling JF - Molecular Pharmacology JO - Mol Pharmacol SP - 502 LP - 513 DO - 10.1124/mol.107.037085 VL - 72 IS - 3 AU - Ute Renner AU - Konstantin Glebov AU - Thorsten Lang AU - Ekaterina Papusheva AU - Saju Balakrishnan AU - Bernhard Keller AU - Diethelm W. Richter AU - Reinhard Jahn AU - Evgeni Ponimaskin Y1 - 2007/09/01 UR - http://molpharm.aspetjournals.org/content/72/3/502.abstract N2 - In the present study, we have used wild-type and palmitoylation-deficient mouse 5-hydroxytryptamine1A receptor (5-HT1A) receptors fused to the yellow fluorescent protein- and the cyan fluorescent protein (CFP)-tagged αi3 subunit of heterotrimeric G-protein to study spatiotemporal distribution of the 5-HT1A-mediated signaling in living cells. We also addressed the question on the molecular mechanisms by which receptor palmitoylation may regulate communication between receptors and Gi-proteins. Our data demonstrate that activation of the 5-HT1A receptor caused a partial release of Gαi protein into the cytoplasm and that this translocation is accompanied by a significant increase of the intracellular Ca2+ concentration. In contrast, acylation-deficient 5-HT1A mutants failed to reproduce both Gαi3-CFP relocation and changes in [Ca2+]i upon agonist stimulation. By using gradient centrifugation and copatching assays, we also demonstrate that a significant fraction of the 5-HT1A receptor resides in membrane rafts, whereas the yield of the palmitoylation-deficient receptor in these membrane microdomains is reduced considerably. Our results suggest that receptor palmitoylation serves as a targeting signal responsible for the retention of the 5-HT1A receptor in membrane rafts. More importantly, the raft localization of the 5-HT1A receptor seems to be involved in receptor-mediated signaling. The American Society for Pharmacology and Experimental Therapeutics ER -