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Rab10 和肌球蛋白 Va 介导脂肪细胞中胰岛素刺激的 GLUT4 储存囊泡转运。

Rab10 and myosin-Va mediate insulin-stimulated GLUT4 storage vesicle translocation in adipocytes.

机构信息

Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.

出版信息

J Cell Biol. 2012 Aug 20;198(4):545-60. doi: 10.1083/jcb.201111091.

DOI:10.1083/jcb.201111091
PMID:22908308
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3514028/
Abstract

Rab proteins are important regulators of insulin-stimulated GLUT4 translocation to the plasma membrane (PM), but the precise steps in GLUT4 trafficking modulated by particular Rab proteins remain unclear. Here, we systematically investigate the involvement of Rab proteins in GLUT4 trafficking, focusing on Rab proteins directly mediating GLUT4 storage vesicle (GSV) delivery to the PM. Using dual-color total internal reflection fluorescence (TIRF) microscopy and an insulin-responsive aminopeptidase (IRAP)-pHluorin fusion assay, we demonstrated that Rab10 directly facilitated GSV translocation to and docking at the PM. Rab14 mediated GLUT4 delivery to the PM via endosomal compartments containing transferrin receptor (TfR), whereas Rab4A, Rab4B, and Rab8A recycled GLUT4 through the endosomal system. Myosin-Va associated with GSVs by interacting with Rab10, positioning peripherally recruited GSVs for ultimate fusion. Thus, multiple Rab proteins regulate the trafficking of GLUT4, with Rab10 coordinating with myosin-Va to mediate the final steps of insulin-stimulated GSV translocation to the PM.

摘要

Rab 蛋白是胰岛素刺激 GLUT4 向质膜(PM)易位的重要调节剂,但特定 Rab 蛋白调节 GLUT4 运输的精确步骤仍不清楚。在这里,我们系统地研究了 Rab 蛋白在 GLUT4 运输中的作用,重点研究了直接介导 GLUT4 储存囊泡(GSV)向 PM 传递的 Rab 蛋白。我们使用双色全内反射荧光(TIRF)显微镜和胰岛素反应性氨肽酶(IRAP)-pHluorin 融合测定法,证明 Rab10 直接促进 GSV 向 PM 的易位和停靠。Rab14 通过含有转铁蛋白受体(TfR)的内体区室介导 GLUT4 向 PM 的传递,而 Rab4A、Rab4B 和 Rab8A 通过内体系统回收 GLUT4。肌球蛋白-Va 通过与 Rab10 相互作用与 GSV 相关联,将外周募集的 GSV 定位用于最终融合。因此,多种 Rab 蛋白调节 GLUT4 的运输,Rab10 与肌球蛋白-Va 协调介导胰岛素刺激的 GSV 向 PM 易位的最后步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/2752d87882cd/JCB_201111091_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/74f618b20848/JCB_201111091_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/10da11f5d657/JCB_201111091_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/cc25dd7fc2ff/JCB_201111091_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/87b0861033f6/JCB_201111091_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/6a8098497efd/JCB_201111091_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/34f11ce52ae1/JCB_201111091_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/de6e2a3a70cb/JCB_201111091_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/2cb4a645e959/JCB_201111091_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/e2a25513edbd/JCB_201111091_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/2752d87882cd/JCB_201111091_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/74f618b20848/JCB_201111091_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/10da11f5d657/JCB_201111091_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/cc25dd7fc2ff/JCB_201111091_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/87b0861033f6/JCB_201111091_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/6a8098497efd/JCB_201111091_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/34f11ce52ae1/JCB_201111091_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/de6e2a3a70cb/JCB_201111091_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/2cb4a645e959/JCB_201111091_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/e2a25513edbd/JCB_201111091_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1289/3514028/2752d87882cd/JCB_201111091_Fig10.jpg

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