Sequence-directed concentration of G protein-coupled receptors in COPII vesicles.

Sequence-directed concentration of G protein-coupled receptors in COPII vesicles.
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G蛋白偶联受体在复合囊泡中的序列定向浓度。

DOI:
10.1016/j.isci.2023.107969
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发表时间:
2023-10-20
期刊:
影响因子:
5.8
通讯作者:
Wu, Guangyu
Wu, Guangyu
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Xu, Xin;Lambert, Nevin A.;Wu, Guangyu

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G蛋白偶联受体(GPCRs)是细胞膜信号蛋白中最大的超家族。然而,几乎没有人知道他们的招聘COPII囊泡在内质网(ER)合成后向前交付。在这里,我们证明了一些GPCR高度集中在ER出口网站(ERES)COPII萌芽之前。血管紧张素II 2型受体(AT 2 R)和CXCR 4浓度分别由一个二酸基序和一个9-残基结构域指导,这些基序也控制受体ER-高尔基体运输。我们进一步表明,AT 2 R与Sar 1 GTdR相互作用,不同的GPCR具有不同的ER-高尔基体转运率通过COPII,这是独立的浓度在ERES。总的来说,这些数据表明,GPCR可以通过特定的基序和与COPII组件的直接相互作用被COPII积极捕获,这反过来又影响了它们的出口动态,并为COPII的目标定位和新生GPCR的前向贩运提供了重要的见解。一些GPCR高度集中在ERES,AT 2 R和CXCR 4向ERES的募集是通过不同的基序介导的,AT 2 R与Sar 1 GT相互作用不同的GPCR通过COPII囊泡具有不同的ER输出动力学细胞生物学;细胞生物学的整合方面;细胞生物学的功能方面
G protein-coupled receptors (GPCRs) constitute the largest superfamily of plasma membrane signaling proteins. However, virtually nothing is known about their recruitment to COPII vesicles for forward delivery after synthesis in the endoplasmic reticulum (ER). Here, we demonstrate that some GPCRs are highly concentrated at ER exit sites (ERES) before COPII budding. Angiotensin II type 2 receptor (AT2R) and CXCR4 concentration are directed by a di-acidic motif and a 9-residue domain, respectively, and these motifs also control receptor ER-Golgi traffic. We further show that AT2R interacts with Sar1 GTPase and that distinct GPCRs have different ER-Golgi transport rates via COPII which is independent of their concentration at ERES. Collectively, these data demonstrate that GPCRs can be actively captured by COPII via specific motifs and direct interaction with COPII components that in turn affects their export dynamics, and provide important insights into COPII targeting and forward trafficking of nascent GPCRs. Some GPCRs are highly concentrated at ERES AT2R and CXCR4 recruitment to ERES are mediated via distinct motifs AT2R interacts with Sar1 GTPase Distinct GPCRs have different ER export kinetics via COPII vesicles Cell biology; Integrative aspects of cell biology; Functional aspects of cell biology
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