Delta opioid receptors recycle to the membrane after sorting to the degradation path
Delta opioid receptors recycle to the membrane after sorting to the degradation path
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DOI：
10.1007/s00018-017-2732-5
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发表时间：
2018-06-01
影响因子：
8
通讯作者：
Pineyro, Graciela
中科院分区：
文献类型：
--
作者：
Charfi, Iness;Abdallah, Khaled;Pineyro, Graciela
内化后不久，δ阿片受体（DOPrs）被G蛋白偶联受体（GPCR）相关结合蛋白降解。在这里，我们提供的证据表明，这一经典的后内吞行程可以纠正下游排序决定，使DOPrs重新获得后，达到晚期内涵体（LE）的膜。LE分选机制涉及ESCRT辅助蛋白阿利克斯和TIP 47/Rab 9修复复合物，其支持受体易位至TGN，随后从TGN重新获得细胞膜。阻止DOPrs完成这一行程沉淀的激动剂DPDPE的急性镇痛耐受，支持这一回收途径的相关性，在维持该受体的镇痛反应。总之，这些发现揭示了内吞后的行程，其中已经被分类降解的GPCR仍然可以再循环到膜。
Soon after internalization delta opioid receptors (DOPrs) are committed to the degradation path by G protein-coupled receptor (GPCR)-associated binding protein. Here we provide evidence that this classical post-endocytic itinerary may be rectified by downstream sorting decisions which allow DOPrs to regain to the membrane after having reached late endosomes (LE). The LE sorting mechanism involved ESCRT accessory protein Alix and the TIP47/Rab9 retrieval complex which supported translocation of the receptor to the TGN, from where it subsequently regained the cell membrane. Preventing DOPrs from completing this itinerary precipitated acute analgesic tolerance to the agonist DPDPE, supporting the relevance of this recycling path in maintaining the analgesic response by this receptor. Taken together, these findings reveal a post-endocytic itinerary where GPCRs that have been sorted for degradation can still recycle to the membrane.