Subtype-Specific Intracellular Trafficking of α2-Adrenergic Receptors

• DOI: 10.1124/mol.51.5.711
• Publication Date: 2018-01-08T20:26:41Z
• Authors: David A. Daunt; Carl Hurt; Lutz Hein; Jaana Kallio; Felix Feng; Brian K. Kobilka
• Keywords: 0301 basic medicine; Molecular Sequence Data; Biological Transport; Fibroblasts; Endoplasmic Reticulum; Immunohistochemistry; Endocytosis; Cell Line; Rats; Mice; 03 medical and health sciences; Dogs; Receptors, Adrenergic, alpha-2; Culture Techniques; COS Cells; Animals; Humans; Amino Acid Sequence

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.