Dopamine D2 receptors form higher order oligomers at physiological expression levels. Export

@article{citeulike:3066955, abstract = {G-protein-coupled receptors are generally thought to be organized as dimers; whether they form higher order oligomers is a topic of much controversy. We combined bioluminescence/fluorescence complementation and energy transfer to demonstrate that at least four dopamine D2 receptors are located in close molecular proximity in living mammalian cells, consistent with their organization as higher order oligomers at the plasma membrane. This implies the existence of multiple receptor interfaces. In addition to the symmetrical interface in the fourth transmembrane segment (TM4) we identified previously by cysteine (Cys) crosslinking, we now show that a patch of residues at the extracellular end of TM1 forms a second symmetrical interface. Crosslinking of D2 receptor with Cys substituted simultaneously into both TM1 and TM4 led to higher order species, consistent with our novel biophysical results. Remarkably, the rate and extent of crosslinking at both interfaces were unaltered over a 100-fold range of receptor expression. Thus, at physiological levels of expression, the receptor is organized in the plasma membrane into a higher order oligomeric structure.}, author = {Guo, Wen and Urizar, Eneko and Kralikova, Michaela and Mobarec, Juan Carlos C. and Shi, Lei and Filizola, Marta and Javitch, Jonathan A.}, citeulike-article-id = {3066955}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/emboj.2008.153}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18668123}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18668123}, day = {3}, doi = {10.1038/emboj.2008.153}, issn = {0261-4189}, journal = {The EMBO journal}, keywords = {crosslinking, dimer, fluorescence, fret, oligomers}, month = {September}, number = {17}, pages = {2293--2304}, posted-at = {2009-10-05 18:52:33}, priority = {2}, publisher = {Nature Publishing Group}, title = {Dopamine D2 receptors form higher order oligomers at physiological expression levels.}, url = {http://dx.doi.org/10.1038/emboj.2008.153}, volume = {27}, year = {2008} }

TY - JOUR ID - citeulike:3066955 L3 - citeulike-article-id:3066955 N2 - G-protein-coupled receptors are generally thought to be organized as dimers; whether they form higher order oligomers is a topic of much controversy. We combined bioluminescence/fluorescence complementation and energy transfer to demonstrate that at least four dopamine D2 receptors are located in close molecular proximity in living mammalian cells, consistent with their organization as higher order oligomers at the plasma membrane. This implies the existence of multiple receptor interfaces. In addition to the symmetrical interface in the fourth transmembrane segment (TM4) we identified previously by cysteine (Cys) crosslinking, we now show that a patch of residues at the extracellular end of TM1 forms a second symmetrical interface. Crosslinking of D2 receptor with Cys substituted simultaneously into both TM1 and TM4 led to higher order species, consistent with our novel biophysical results. Remarkably, the rate and extent of crosslinking at both interfaces were unaltered over a 100-fold range of receptor expression. Thus, at physiological levels of expression, the receptor is organized in the plasma membrane into a higher order oligomeric structure. IS - 17 JF - The EMBO journal SN - 0261-4189 EP - 2304 TI - Dopamine D2 receptors form higher order oligomers at physiological expression levels. PB - Nature Publishing Group VL - 27 SP - 2293 KW - crosslinking KW - dimer KW - fluorescence KW - fret KW - oligomers AU - Guo, Wen AU - Urizar, Eneko AU - Kralikova, Michaela AU - Mobarec, Juan Carlos AU - Shi, Lei AU - Filizola, Marta AU - Javitch, Jonathan PY - 2008/09/03/ UR - http://dx.doi.org/10.1038/emboj.2008.153 ER -