Endo-lysosomal sorting of G-protein-coupled receptors by ubiquitin: Diverse pathways for G-protein-coupled receptor destruction and beyond.
Endo-lysosomal sorting of G-protein-coupled receptors by ubiquitin: Diverse pathways for G-protein-coupled receptor destruction and beyond.
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DOI：
10.1111/tra.12619
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Trejo J
中科院分区：
文献类型：
--
作者：
Dores MR;Trejo J
泛素以单个泛素部分或多聚泛素链的形式共价连接到底物蛋白质上，并且通常与蛋白质降解有关，然而，不同类型的泛素连接也用于控制其他关键的细胞过程，如细胞信号传导。据报道，超过40种哺乳动物G蛋白偶联受体（GPCR）被泛素化，但尽管GPCR信号转导的多样性和丰富的复杂性，泛素在很大程度上归因于受体降解。事实上，GPCR泛素化靶向受体，由溶酶体降解，这是由ESCRT机制和蛋白酶体介导的。这导致了这样的观点，即泛素和ESCRT主要起着靶向GPCR进行破坏的信号的作用。与这种传统观点相反，研究表明，某些GPCR和典型的泛素结合ESCRT的泛素化不是受体降解所必需的，并揭示了存在多种复杂的途径来调节GPCR的内-溶酶体分选。在其他研究中，GPCR泛素化已被证明驱动信号而不是受体降解，并进一步揭示了GPCR触发泛素化机制活性的机制的新见解。在这里，我们讨论了泛素控制GPCR内溶酶体分选和超越的不同途径。GPCR和内吞衔接蛋白的泛素化促进GPCR运输到溶酶体，此外，GPCR和GPCR效应子的泛素化可以介导特定信号通路的激活。GPCR泛素化对于靶向一些GPCR以供蛋白酶体降解也是至关重要的。这篇综述强调了泛素控制GPCR内溶酶体分选和信号传导的多种途径，这些途径扩展了泛素在调节GPCR生物学中的功能。
Ubiquitin is covalently attached to substrate proteins in the form of a single ubiquitin moiety or polyubiquitin chains and has been generally linked to protein degradation, however, distinct types of ubiquitin linkages are also used to control other critical cellular processes like cell signaling. Over forty mammalian G protein-coupled receptors (GPCRs) have been reported to be ubiquitinated, but despite the diverse and rich complexity of GPCR signaling, ubiquitin has been largely ascribed to receptor degradation. Indeed, GPCR ubiquitination targets the receptors for degradation by lysosome, which is mediated by the ESCRT machinery, and the proteasome. This has led to the view that ubiquitin and ESCRTs primarily function as the signal to target GPCRs for destruction. Contrary to this conventional view, studies indicate that ubiquitination of certain GPCRs and canonical ubiquitin-binding ESCRTs are not required for receptor degradation and revealed that diverse and complex pathways exist to regulate endo-lysosomal sorting of GPCRs. In other studies, GPCR ubiquitination has been shown to drive signaling and not receptor degradation and further revealed novel insight into the mechanisms by which GPCRs trigger the activity of the ubiquitination machinery. Here, we discuss the diverse pathways by which ubiquitin controls GPCR endo-lysosomal sorting and beyond. Ubiquitination of GPCRs and endocytic adaptor proteins facilitates GPCR trafficking to lysosomes and. In addition, ubiquitination of GPCRs and GPCR effectors can mediate the activation of specific signaling pathways. GPCR ubiquitination is also critical for targeting some GPCRs for degradation by proteasomes. This review highlights the multiple pathways by which ubiquitin controls GPCR endo-lysosomal sorting and signaling, which expand the function of ubiquitin in regulating GPCR biology.
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影响因子：
--
作者：
El Buri A;Adams DR;Smith D;Tate RJ;Mullin M;Pyne S;Pyne NJ
通讯作者：
Pyne NJ
影响因子：
4.8
作者：
Groer, Chad E.;Schmid, Cullen L.;Bohn, Laura M.
通讯作者：
Bohn, Laura M.
DOI：
10.1083/jcb.201110031
发表时间：
2012-04-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
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通讯作者：
Trejo J
影响因子：
8
作者：
Charfi, Iness;Abdallah, Khaled;Pineyro, Graciela
通讯作者：
Pineyro, Graciela
影响因子：
11.8
作者：
Dowlatshahi, Dara P.;Sandrin, Virginie;Kopito, Ron R.
通讯作者：
Kopito, Ron R.