Subtype-specific intracellular trafficking of alpha2-adrenergic receptors.
The three alpha2-adrenergic receptor subtypes (alpha2a, alpha2b, and alpha2c) are highly homologous G protein-coupled receptors. These receptors all couple to pertussis toxin-sensitive G proteins and have relatively similar pharmacological properties. To further explore functional differences between these receptors, we used immunocytochemical techniques to compare the ability of the three alpha2-receptor subtypes to undergo agonist-mediated internalization. The alpha2a-receptor does not internalize after agonist treatment. In contrast, we observed that the alpha2b-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by the beta2-adrenergic receptor. Attempts to examine internalization of the alpha2c-receptor were complicated by the fact that the majority of the alpha2c receptor resides in the endoplasmic reticulum and cis/media Golgi and there is relatively little cell surface localization. Nevertheless, we were able to detect some internalization of the alpha2c-receptor after prolonged agonist treatment. However, we observed no significant movement of alpha2c-receptor from the intracellular pool to the plasma membrane during a 4-hr treatment of cells with cycloheximide, suggesting that these cells are unable to process alpha2c-receptors in the same way they process the alpha2a or alpha2b subtypes.
Daunt
D A
DA
Department of Molecular and Cellular Physiology, Stanford University, California 94305, USA.
Hurt
C
C
Hein
L
L
Kallio
J
J
Feng
F
F
Kobilka
B K
BK
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D019556:COS Cells; D002460:Cell Line; D046508:Culture Techniques; D004285:Dogs; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000145:classification / Q000378:metabolism*
D018341:Receptors, Adrenergic, alpha-2