Localization of the mouse 5-hydroxytryptamine(1A) receptor in lipid microdomains depends on its palmitoylation and is involved in receptor-mediated signaling. Export

@article{citeulike:3508683, abstract = {In the present study, we have used wild-type and palmitoylation-deficient mouse 5-hydroxytryptamine(1A) receptor (5-HT1A) receptors fused to the yellow fluorescent protein- and the cyan fluorescent protein (CFP)-tagged alpha(i3) 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 G(i)-proteins. Our data demonstrate that activation of the 5-HT1A receptor caused a partial release of Galpha(i) protein into the cytoplasm and that this translocation is accompanied by a significant increase of the intracellular Ca(2+) concentration. In contrast, acylation-deficient 5-HT1A mutants failed to reproduce both Galpha(i3)-CFP relocation and changes in [Ca(2+)](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.}, author = {Renner, U. and Glebov, K. and Lang, T. and Papusheva, E. and Balakrishnan, S. and Keller, B. and Richter, D. W. and Jahn, R. and Ponimaskin, E.}, citeulike-article-id = {3508683}, citeulike-linkout-0 = {http://dx.doi.org/10.1124/mol.107.037085}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/17540717}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=17540717}, doi = {10.1124/mol.107.037085}, issn = {0026-895X}, journal = {Molecular pharmacology}, keywords = {5-ht1, localization, microdomains}, month = {September}, number = {3}, pages = {502--513}, posted-at = {2008-11-13 14:07:14}, priority = {2}, title = {Localization of the mouse 5-hydroxytryptamine(1A) receptor in lipid microdomains depends on its palmitoylation and is involved in receptor-mediated signaling.}, url = {http://dx.doi.org/10.1124/mol.107.037085}, volume = {72}, year = {2007} }

TY - JOUR ID - citeulike:3508683 L3 - citeulike-article-id:3508683 N2 - In the present study, we have used wild-type and palmitoylation-deficient mouse 5-hydroxytryptamine(1A) receptor (5-HT1A) receptors fused to the yellow fluorescent protein- and the cyan fluorescent protein (CFP)-tagged alpha(i3) 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 G(i)-proteins. Our data demonstrate that activation of the 5-HT1A receptor caused a partial release of Galpha(i) protein into the cytoplasm and that this translocation is accompanied by a significant increase of the intracellular Ca(2+) concentration. In contrast, acylation-deficient 5-HT1A mutants failed to reproduce both Galpha(i3)-CFP relocation and changes in [Ca(2+)](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. IS - 3 JF - Molecular pharmacology SN - 0026-895X EP - 513 TI - Localization of the mouse 5-hydroxytryptamine(1A) receptor in lipid microdomains depends on its palmitoylation and is involved in receptor-mediated signaling. VL - 72 SP - 502 KW - 5-ht1 KW - localization KW - microdomains AU - Renner, U AU - Glebov, K AU - Lang, T AU - Papusheva, E AU - Balakrishnan, S AU - Keller, B AU - Richter, DW AU - Jahn, R AU - Ponimaskin, E PY - 2007/09// UR - http://dx.doi.org/10.1124/mol.107.037085 ER -