Homodimerization of the beta 2-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...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-08, Vol.279 (32), p.33390-33397
Main Authors: Salahpour, Ali, Angers, Stephane, Mercier, Jean-Francois, Lagace, Monique, Marullo, Stefano, Bouvier, Michel
Format: Article
Language:English
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Summary: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 beta 2-adrenergic receptor ( beta 2AR) 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, beta 2AR 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, super(276)GXXXGXXXL super(284), prevented normal trafficking of the receptor to the plasma membrane. Taken together, these data indicate that beta 2AR homodimerization plays an important role in ER export and cell surface targeting.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M403363200