G蛋白偶联受体相关分选蛋白功能特征与相关疾病研究进展

doi:10.16288/j.yczz.20-020

遗传 ›› 2020, Vol. 42 ›› Issue (8): 713-724.doi: 10.16288/j.yczz.20-020

• 综述 • 下一篇

G蛋白偶联受体相关分选蛋白功能特征与相关疾病研究进展

张敏, 梁丽鸿, 鲁雅洁(), 曹新

南京医科大学医学遗传学系,南京 211166

收稿日期:2020-02-19 修回日期:2020-04-16 出版日期:2020-08-20 发布日期:2020-05-19
通讯作者: 鲁雅洁 E-mail:luyajie@njmu.edu.cn
作者简介:张敏,在读硕士研究生,专业方向：遗传学。E-mail: zmzhangmin@njmu.edu.cn
基金资助:
国家自然科学基金项目编号(31571302);江苏省财政厅转化医学实验室平台建设项目资助

G protein-coupled receptor-associated sorting proteins: function and relevant disorders

Min Zhang, Lihong Liang, Yajie Lu(), Xin Cao

Department of Medical Genetics, Nanjing Medical University, Nanjing 211166, China

Received:2020-02-19 Revised:2020-04-16 Online:2020-08-20 Published:2020-05-19
Contact: Lu Yajie E-mail:luyajie@njmu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China No(31571302);Jiangsu Key Laboratory of Xenotransplantation

摘要/Abstract

摘要：

G蛋白偶联受体(G protein-coupled receptors, GPCRs)作为最大的一类膜蛋白受体家族,可被多种配体激活并发挥相应的信号转导功能,参与生物体内重要的生理过程。G蛋白偶联受体相关分选蛋白(G protein-coupled receptors associated sorting proteins, GASPs)则对内吞后的GPCRs分选过程发挥着重要的作用,并介导受体进入降解或再循环途径,进而调控细胞的信号转导等过程。研究发现GASPs的功能缺陷与多种疾病相关,包括神经系统疾病、肿瘤和耳聋等。本文重点介绍了G蛋白偶联受体相关分选蛋白的功能特征及其相关信号通路,描述了GASPs功能缺陷与疾病的关联性及家族蛋白与GPCRs的相互作用、GASPs分选途径的发现、参与的信号通路及对基因转录调控,以期为GASPs相关多种疾病的治疗提供新的思路和策略。

关键词: G蛋白偶联受体, G蛋白偶联受体相关分选蛋白, 信号转导, 疾病

Abstract:

G protein-coupled receptors (GPCRs), the largest family of membrane protein receptors, can be activated by a variety of ligands and participate in signaling transduction, and they are essential in the physiologic process in vivo. GPCR-associated sorting proteins (GASPs) play an important role in the post-endocytic sorting of GPCRs. They mediate the degradation or recycling pathway, and regulate cell signaling transduction and other biological processes. The functional defects of GASPs have been reported to be implicated in pathogenesis of some neurological diseases, tumors and deafness and so on. In this review, we summarize the GASPs’ function, GPCR-GASP interactions, GPCR sorting pathway and GASP-related signaling pathways implicated in the transcriptional regulation. It could help to understand the potential linkage between GASPs’ dysfunction and diseases, and provide a new approach and strategy for the treatment of GASP-related diseases.

Key words: G protein-coupled receptors (GPCRs), G protein-coupled receptor-associated sorting proteins (GASPs), signal transduction, disease

张敏, 梁丽鸿, 鲁雅洁, 曹新. G蛋白偶联受体相关分选蛋白功能特征与相关疾病研究进展[J]. 遗传, 2020, 42(8): 713-724.

Min Zhang, Lihong Liang, Yajie Lu, Xin Cao. G protein-coupled receptor-associated sorting proteins: function and relevant disorders[J]. Hereditas(Beijing), 2020, 42(8): 713-724.

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GASPs	别名	互作伴侣	结合位点			主要功能	参考文献
GASPs	别名	互作伴侣	氨基末端	羧基末端	GASP基序	主要功能	参考文献
GASP-1	PIPS/KIAA0443	GPCRs		√	√	参与转运和降解	[25]
		Period 1	√		√	与昼夜节律调控相关	[38]
		Gab 1	结合位点尚未明确			与生长发育相关	[39]
		Microtubules		√	√	维持细胞骨架相关	[32]
GASP-2	HIP15	GPCRs		√	√	参与转运和降解	[30]
		Htt		√		与亨廷顿舞蹈症相关	[40]
		Smoothened		√		参与Hedgehog信号通路	[41]
		mGluR5		√		与自闭症有关	[42]
GASP-3	P60TRP/BHLHB9	GPCRs		√	√	参与转运和降解	[28]
		PPP2R5E	结合位点尚未明确			与神经元的生长调节有关	[43]
		IPO5	结合位点尚未明确			与神经元的生长调节有关	[43]
GASP-5	ARMCX5	GPCRs		√	√	参与转运和降解	[28]
GASP-6	ALEX3/ARMCX3	Sox10		√		与转录有关	[44]
GASP-7	ALEX1/ARMCX1	GPCRs		√		参与转运和降解	[28]
GASP-7	ALEX1/ARMCX1	PP110	结合位点尚未明确			与肿瘤的发生和发展有关	[29]
GASP-8	SVH	P53		√		与肿瘤的发生和发展有关	[37]
GASP-9	ALEX2/ARMCX2	VIM	结合位点尚未明确			维持细胞骨架相关	[33]

G蛋白偶联受体相关分选蛋白功能特征与相关疾病研究进展

G protein-coupled receptor-associated sorting proteins: function and relevant disorders

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