title: The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane.
abstract: The literature on GPCR (G-protein-coupled receptor) homo-oligomerization encompasses conflicting views that range from interpretations that GPCRs must be monomeric, through comparatively newer proposals that they exist as dimers or higher-order oligomers, to suggestions that such quaternary structures are rather ephemeral or merely accidental and may serve no functional purpose. In the present study we use a novel method of FRET (Förster resonance energy transfer) spectrometry and controlled expression of energy donor-tagged species to show that M(3)Rs (muscarinic M(3) acetylcholine receptors) at the plasma membrane exist as stable dimeric complexes, a large fraction of which interact dynamically to form tetramers without the presence of trimers, pentamers, hexamers etc. That M(3)R dimeric units interact dynamically was also supported by co-immunoprecipitation of receptors synthesized at distinct times. On the basis of all these findings, we propose a conceptual framework that may reconcile the conflicting views on the quaternary structure of GPCRs.
authors.affiliation: Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA.
authors.forename: Suparna
authors.initials: S
authors.lastname: Patowary
authors.forename: Elisa
authors.initials: E
authors.lastname: Alvarez-Curto
authors.forename: Tian-Rui
authors.initials: TR
authors.lastname: Xu
authors.forename: Jessica D
authors.initials: JD
authors.lastname: Holz
authors.forename: Julie A
authors.initials: JA
authors.lastname: Oliver
authors.forename: Graeme
authors.initials: G
authors.lastname: Milligan
authors.forename: Valerică
authors.initials: V
authors.lastname: Raicu
mesh_terms: D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer / Q000379:methods; D057809:HEK293 Cells; D006801:Humans; D008958:Models, Molecular; D055503:Protein Multimerization / Q000235:genetics; D055550:Protein Stability; D020836:Protein Structure, Quaternary / Q000235:genetics; D043587:Receptor, Muscarinic M3 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D043587:Receptor, Muscarinic M3; D011993:Recombinant Fusion Proteins