Regulation of oligomeric organization of the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor observed by spatial intensity distribution analysis.

摘要: The questions of whether G protein-coupled receptors exist as monomers, dimers, and/or oligomers and if these species interconvert in a ligand-dependent manner are among the most contentious current issues biology. When employing spatial intensity distribution analysis to laser scanning confocal microscope images cells stably expressing either plasma membrane-associated form monomeric enhanced green fluorescent protein (eGFP) or tandem version this fluorophore, eGFP was identified dimer. Similar studies on an eGFP-tagged epidermal growth factor receptor demonstrated that, although largely monomer basal state, rapidly became predominantly dimeric upon addition its ligand factor. In induced express serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor, global construct quantal brightness consistent with predominant being dimeric. However, detailed presence multiple forms ranging from monomers higher-order oligomers. Furthermore, treatment chemically distinct 5-HT2C antagonists resulted time-dependent change quaternary organization one which there preponderance monomers. This antagonist-mediated effect reversible, because washout regeneration many oligomeric receptor.