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| μ-鸦片受体磷酸化状态通过Rab4和Rab11途径决定了受体替代性再循环 |
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| Phosphorylation state of μ-opioid receptor determines the alternative recycling of receptor via Rab4 or Rab11 pathway |
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| Wang F., Chen X., Zhang X., Ma L. 2009/5/29 18:38:57 |
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Molecular Endocrinology, 2008, Volume 22, Issue 8
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| Agonist-induced phosphorylation, internalization, and intracellular trafficking of G protein-coupled receptors are critical in regulating both cellular responsiveness and signal transduction. The current study investigated the role of receptor phosphorylation state in regulation of agonist-induced internalization and intracellular trafficking of μ-opioid receptor (MOR). Our results showed that after agonist stimulation, the recycle of a mutant MOR that lacks the C-terminal residues after Asn362 (MOR362T) was greatly decreased, whereas a C-terminal phosphorylation sites-mutated MOR (MOR3A), which is deficient in agonist-induced phosphorylation recycled back to the membrane at a level comparable to that of the wild-type receptor, however, interestingly at a slower rate. Inhibition of functions of either Rab4 or Rab11 by dominant-negative mutants and small interfering RNA both significantly impaired the recycling of the wild-type MOR, whereas the recycling of the phosphorylation-deficient mutant was only inhibited by the dominant-negative mutant and small interfering RNA of Rab11, suggesting that the recycling of nonphosphorylated MOR is exclusively via Rab11-mediated pathway. Furthermore, phosphorylated MOR was observed accumulated in Rab5- and Rab4-, but not Rab11 -positive vesicles. Our data indicate that both phosphorylated and nonphosphorylated MOR internalize via Rab5-dependent pathway after agonist stimulation, and the phosphorylated and nonphosphorylated MORs recycle through distinct vesicular trafficking pathways mediated by Rab4 and Rab11, respectively, which may ultimately lead to differential cellular responsiveness or downstream signaling. Copyright © 2008 by The Endocrine Society. |
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| Correspondence Address: Ma, L.; Pharmacology Research Center, Fudan University, 138 YiXue Yuan Road, Shanghai 200032, China; email: lanma@fudan.edu.cn |
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 疾病资源中心
摘自：《西氏内科学》，第23版
患者女性，21岁，因干咳、间歇性气促2个月到急诊科就诊。开始症状为上呼吸道感染引起的鼻塞、流涕和咳嗽。医生检查后开了抗生素。服药后鼻部症状缓解，但仍有轻微干咳和呼吸困难。其他症状包括疲劳和焦虑。否认发热、体重减轻、胸痛、端坐呼吸、气喘、鼻后滴漏、胃灼热以及神经系统症状。
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