Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell surface targeting.
Although homodimerization has been demonstrated for a large number of G protein-coupled receptors (GPCRs), no general role has been attributed to this process. Because it is known that oligomerization plays a key role in the quality control and endoplasmic reticulum (ER) export of many proteins, we sought to determine if homodimerization could play such a role in GPCR biogenesis. Using the beta2-adrenergic receptor (beta2AR) as a model, cell fractionation studies revealed that receptor homodimerization is an event occurring as early as the ER. Supporting the hypothesis that receptor homodimerization is involved in ER processing, beta2AR mutants lacking an ER-export motif or harboring a heterologous ER-retention signal dimerized with the wild-type receptor and inhibited its trafficking to the cell surface. Finally, in addition to inhibiting receptor dimerization, disruption of the putative dimerization motif, 276GXXXGXXXL284, prevented normal trafficking of the receptor to the plasma membrane. Taken together, these data indicate that beta2AR homodimerization plays an important role in ER export and cell surface targeting.
Salahpour
Ali
A
Department of Biochemistry and Groupe de Recherche sur le Système Nerveux Autonome, Université de Montréal, Montréal, Quebec H3C 3J7, Canada.
Angers
Stéphane
S
Mercier
Jean-François
JF
Lagacé
Monique
M
Marullo
Stefano
S
Bouvier
Michel
M
D001665:Binding Sites; D001692:Biological Transport; D002458:Cell Fractionation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004735:Energy Transfer; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006388:Hemagglutinins / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D008163:Luminescent Measurements; D008164:Luminescent Proteins / Q000235:genetics; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D018343:Receptors, Adrenergic, beta-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D013329:Structure-Activity Relationship; D014162:Transfection
D006388:Hemagglutinins; D008164:Luminescent Proteins; D018343:Receptors, Adrenergic, beta-2; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D008156:Luciferases