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中华肺部疾病杂志(电子版) ›› 2022, Vol. 15 ›› Issue (05) : 754 -758. doi: 10.3877/cma.j.issn.1674-6902.2022.05.039

综述

Rab蛋白调控肺巨噬细胞功能的研究进展
孙芬芬1, 代洋1, 李力1,()   
  1. 1. 400010 重庆,陆军特色医学中心(大坪医院)呼吸与危重症医学科
  • 收稿日期:2022-05-11 出版日期:2022-10-25
  • 通信作者: 李力
  • 基金资助:
    陆军军医大学优青人才培养基金

Progress in regulation of Rab protein regulating lung macrophage function

Fenfen Sun1, Yang Dai1, Li Li1()   

  • Received:2022-05-11 Published:2022-10-25
  • Corresponding author: Li Li
引用本文:

孙芬芬, 代洋, 李力. Rab蛋白调控肺巨噬细胞功能的研究进展[J]. 中华肺部疾病杂志(电子版), 2022, 15(05): 754-758.

Fenfen Sun, Yang Dai, Li Li. Progress in regulation of Rab protein regulating lung macrophage function[J]. Chinese Journal of Lung Diseases(Electronic Edition), 2022, 15(05): 754-758.

Rab蛋白是一类Ras蛋白超家族成员。目前在人类细胞中发现了44个Rab GTPases,多数进化保守,从真核细胞共同祖先(last eukaryotic common ancestor, LECA)到人类未发生过改变[1]。它最主要的作用是调控细胞内膜转运系统(intracellular membrane trafficking system)中囊泡的转运、黏附、锚定、融合等阶段。细胞内膜转运系统主要是将胞内的蛋白质等成分用囊泡包裹起来,如将蛋白/多肽通过囊泡分泌到胞外、胞吞外来物质(如营养物质等)、新生成的蛋白质用囊泡转运到目的细胞器(如高尔基体到细胞膜),或将与细胞膜上受体包裹后内化。通过调控特定蛋白到达目的细胞器的数量及质粒,调控细胞生长、压力下反应及病理改变。Rab GTPase通过调控细胞内特定蛋白的转运过程,发挥调控细胞生理/病理功能的作用。

表1 部分Rab GTPase调控囊泡转运的作用及生物学效应
Rab蛋白名称 调控囊泡转运 涉及的细胞生物学效应
Rab1 (1)将β-肾上腺素受体(β-AR)从内质网转运至高尔基体 (1)调控大鼠肺微血管内皮细胞渗透性[21]
(2)将血管紧张素Ⅱ 1型受体(angiotensin Ⅱ type 1 receptor,AT1R)从内质网转运至高尔基体 (2)调控大鼠肺动脉平滑肌细胞的表型转换[22]
(3)介导自噬体(autophageosme)形成[23]
(3)调控未知 (4)介导自噬体形成和促进自噬[24]
(4) Rab1a通过C9orf72介导ULK1复合物从吞噬泡转移至初始自噬体 (5)调控血管紧张素Ⅱ(ATⅡ)介导的ERK1/2通路[25]
(6)调控新生鼠心肌细胞的增殖[26]
(5)将新合成的血管紧张素Ⅱ 1型受体(AT2R)从内质网转运至细胞膜 (7)调控CaR细胞膜水平以及对钙离子的敏感性[27]
(6)将β2-AR和α1b-AR从内质网转运至细胞膜  
(7)将钙敏感受体(calcium-sensing receptor, CaR)从内质网转运至高尔基体  
Rab2 (1)在高尔基体处Rab2与GOLGA2,并将ULK1转运到吞噬泡表面,并促进吞噬体形成 (1)介导自噬体形成和促进自噬[28]
(2)将AT1R从高尔基体转运至内质网 (2)减少细胞膜表面AT1R的水平[29]
Rab3和Rab27 (1)介导钙离子的外分泌 (1)促进大鼠海马神经元高K+诱导的生长因子释放[30]
(2)介导胰岛素的外分泌 (2)促进小鼠β胰腺细胞释放胰岛素[31,32]
(3)介导谷氨酸释放? (3)促进小鼠突触释放谷氨酸[33]
(4)介导精液中致密核心颗粒(dense-core granule)释放 (4)促进精液中精液中致密核心颗粒释放[34]
Rab4 (1)介导亨廷顿基因(huntingtin, HTT)在轴突上双向转运 (1)抑制HTT-Rab4的转运,导致纹状神经元的损害和亨廷顿病[35]
(2)介导VEGFR2从细胞膜内化进入早期内涵体 (2)调控血管生成[36]
(3)介导P-糖蛋白(P-glycoprotein)从胞内转运到细胞膜 (3)参与K562细胞多药耐药[37]
(4)介导β2-AR从细胞膜至早期内涵体 (4)抑制肾上腺素致心肌细胞的再致敏以及调控心肌的收缩性[38]
(5)将转铁蛋白受体(transferrin receptor, Tfn-R)从内涵体再次循环转运到细胞膜 (5)调控Tfn-R的胞内循环[39]
Rab5 (1)介导β2-AR从细胞膜内化进入早期内涵体 (1)调控肺微血管内皮细胞渗透性[40]
(2)介导内涵体与线粒体融合 (2)调控细胞氧化应激与线粒体质量[41]
Rab7 (1)绑定Arl8b,促进晚期溶酶体与溶酶体的融合 (1)调控巨噬细胞的吞噬功能及细胞自噬[42]
(2)调控损伤线粒体与溶酶体融合 (2)调控细胞自稳态[43],保护心肌细胞[44]
(3)通过调控NRBF2,调控自噬体的成熟及与溶酶体的融合 (3)调控细胞自噬,促进阿尔兹海默症相关蛋白的降解[45]
Rab10 (1)调控胞饮泡与内涵体融合 (1)调控巨噬细胞的吞噬功能[46]
(2)介导GLUT4从高尔基转运到细胞膜 (2)调控胰岛素介导的葡萄糖转运[47,48]
(3)将TLR4从高尔基体转运至细胞膜 (3)促进LPS诱导的巨噬细胞炎症反应和急性肺损伤[49]
Rab11 (1)将多药耐药基因(multidrug resistance-associated protein,MRP)2从细胞浆转运至细胞膜 (1)调控肿瘤耐药[50]
(2)将CI-M6PR(cation-independent mannose 6-phosphatereceptor)转运至循环内涵体,进而再次回到细胞膜上 (2)维持细胞内稳态[51,52]
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