Subtype-specific differences in the intracellular sorting of G protein-coupled receptors.
We have examined the subcellular distribution of three subtypes of adrenergic receptor by immunocytochemical localization of wild-type and epitope-tagged proteins expressed in Cos-7 and K293 cells. Two subtypes (beta 2 and M alpha 2-10H) are localized in the plasma membrane at steady state in untreated cells, while another subtype (M alpha 2-4H) is found both in the plasma membrane and in a population of intracellular vesicles. Within 15 min following the addition of adrenergic agonists, beta 2 and M alpha 2-10H receptors are differentially sorted; beta 2 receptors are selectively internalized to intracellular vesicles, which are distinct from those containing M alpha 2-4H receptors, while M alpha 2-10H receptors remain in the plasma membrane. Subtype-specific sorting suggests a new class of functional properties that may differentiate the signaling and regulation of homologous G protein-coupled receptors.
von Zastrow
M
M
Howard Hughes Medical Institute, Stanford University, California 94305.
Link
R
R
Daunt
D
D
Barsh
G
G
Kobilka
B
B
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D000939:Epitopes / Q000032:analysis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005818:Genetic Engineering; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008969:Molecular Sequence Data; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D000939:Epitopes; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D019204:GTP-Binding Proteins; D007545:Isoproterenol