Cell-surface targeting of alpha2-adrenergic receptors -- inhibition by a transport deficient mutant through dimerization.
Cell Signal
; 18(3): 318-27, 2006 Mar.
Article
em En
| MEDLINE
| ID: mdl-15961277
ABSTRACT
We previously demonstrated that the alpha2B-adrenergic receptor mutant, in which the F(x)6IL motif in the membrane-proximal carboxyl terminus were mutated to alanines (alpha2B-ARm), is deficient in export from the endoplasmic reticulum (ER). In this report, we determined if alpha2B-ARm could modulate transport from the ER to the cell surface and signaling of its wild-type counterpart. Transient expression of alpha2B-ARm in HEK293T cells markedly inhibited cell-surface expression of wild-type alpha2B-AR, as measured by radioligand binding. Subcellular localization demonstrated that alpha2B-ARm trapped alpha2B-AR in the ER. The alpha2B-AR was shown to form homodimers and heterodimers with alpha2B-ARm as measured by co-immunoprecipitation of the receptors tagged with green fluorescent protein and hemagglutinin epitopes. In addition to alpha2B-AR, the transport of alpha2A-AR and alpha2C-AR to the cell surface was also inhibited by alpha2B-ARm. Furthermore, transient expression of alpha2B-ARm significantly reduced cell-surface expression of endogenous alpha2-AR in NG108-15 and HT29 cells. Consistent with its effect on alpha2-AR cell-surface expression, alpha2B-ARm attenuated alpha2A-AR- and alpha2B-AR-mediated ERK1/2 activation. These data demonstrated that the ER-retained mutant alpha2B-ARm conferred a dominant negative effect on the cell-surface expression of wild-type alpha2-AR, which is likely mediated through heterodimerization. These data indicate a crucial role of ER export in the regulation of cell-surface targeting and signaling of G protein-coupled receptors.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Membrana Celular
/
Receptores Adrenérgicos alfa 2
/
Retículo Endoplasmático
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Mutação
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Signal
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos