The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs.

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs.
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DOI:
10.1016/j.celrep.2017.10.011
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发表时间:
2017-10-24
期刊:
影响因子:
8.8
通讯作者:
Wu G
Wu G
中科院分区:
生物学1区
文献类型:
--
作者:
Li C;Wei Z;Fan Y;Huang W;Su Y;Li H;Dong Z;Fukuda M;Khater M;Wu G

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G蛋白偶联受体(GPCR)是细胞表面信号蛋白中最大的超家族。然而,其表面靶向和分选的机制知之甚少。在这里,我们筛选的Rab家族的小GTP酶的表面运输的多个GPCR。我们发现,Rab 43功能的操纵显着改变了所有GPCR研究的表面呈现和信号,而不影响非GPCR膜蛋白。Rab 43特异性地调节新生GPCR从内质网(ER)到高尔基体的转运。更有趣的是,Rab 43以激活依赖的方式直接与GPCR相互作用。在受体中鉴定的Rab 43结合结构域有效地将非GPCR膜蛋白转运转化为Rab 43依赖性途径。这些数据揭示了Rab 43在新生GPCR的顺行ER-高尔基体运输中的关键作用,以及凭借其直接相互作用的能力对GPCR成员进行ER分选。Li等报道Rab 43 GTdR控制新生GPCR的顺行ER-高尔基体转运,以及它们从其他膜蛋白中分选,这是通过与受体的直接相互作用介导的。他们的结果表明了GPCR超家族成员的靶向和分选机制。
G-protein-coupled receptors (GPCRs) constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER) to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly. Li et al. report that Rab43 GTPase controls anterograde ER-Golgi transport of nascent GPCRs, as well as their sorting from other membrane proteins, which is mediated via direct interaction with the receptors. Their results suggest a mechanism of targeting and sorting of the members of the GPCR superfamily.
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