Subtype-specific intracellular trafficking of alpha(2)-adrenergic receptors
Subtype-specific intracellular trafficking of alpha(2)-adrenergic receptors
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DOI：
10.1124/mol.51.5.711
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发表时间：
1997-05-01
影响因子：
3.6
通讯作者：
Kobilka, BK
中科院分区：
文献类型：
--
作者：
Daunt, DA;Hurt, C;Kobilka, BK
三种α（2）肾上腺素能受体亚型（α（2a）、α（2b）和α（2c））是高度同源的G蛋白偶联受体。这些受体都与百日咳毒素敏感的G蛋白偶联，并具有相对相似的药理学特性。为了进一步探索这些受体之间的功能差异，我们使用免疫细胞化学技术来比较三种α（2）受体亚型进行激动剂介导的内化的能力。α（2a）-受体在激动剂处理后不内化。相反，我们观察到α（2b）-受体能够经历激动剂诱导的内化，并且似乎遵循与β（2）-肾上腺素能受体相同的内体途径，由于大多数α（2c）受体存在于内质网中，顺/顺式表达，内侧高尔基体和有相对较少的细胞表面定位。然而，我们能够检测到一些内在的α（2c）受体后，长期激动剂治疗。然而，在用放线菌酮处理细胞4小时期间，我们没有观察到α（2c）-受体从细胞内池到质膜的显著运动，这表明这些细胞不能以与它们处理α（2a）或α（2b）亚型相同的方式处理α（2c）-受体。
The three alpha(2)-adrenergic receptor subtypes (alpha(2a), alpha(2b), and alpha(2c)) 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 alpha(2)-receptor subtypes to undergo agonist-mediated internalization. The alpha(2a)-receptor does not internalize after agonist treatment. In contrast, we observed that the alpha(2b)-receptor is able to undergo agonist-induced internalization and seems to follow the same endosomal pathway used by the beta(2)-adrenergic receptor, Attempts to examine internalization of the alpha(2c)-receptor were complicated by the fact that the majority of the alpha(2c)-receptor resides in the endoplasmic reticulum and cis/medial Golgi and there is relatively little cell surface localization. Nevertheless, we were able to detect some internalization of the alpha(2c)-receptor after prolonged agonist treatment. However, we observed no significant movement of alpha(2c)-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 alpha(2c)-receptors in the same way they process the alpha(2a) or alpha(2b) subtypes.