Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.
Regulated dynamic subcellular GLUT4 localization revealed by proximal proteome mapping in human muscle cells.
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DOI：
10.1242/jcs.261454
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发表时间：
2023-12-01
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
作者：
葡萄糖转运的调节是控制全身代谢的核心，由脂肪和肌肉细胞质膜（PM）中GLUT 4葡萄糖转运蛋白（也称为SLC 2A4）的量决定。生理信号[如激活的胰岛素受体或AMP激活的蛋白激酶（AMPK）]增加PM GLUT 4。在这里，我们表明，PM和人体肌肉细胞内部之间的GLUT4的分布是动态维持的，AMPK通过调节胞吐和胞吞作用促进PM GLUT4的再分配。AMPK对胞吐的刺激由Rab10和Rab GTP酶激活蛋白TBC1D4介导。APEX2邻近映射显示，GLUT4在未受刺激的肌细胞中穿过PM近端和PM远端隔室，进一步支持GLUT4通过组成性检索机制的保留。AMPK刺激的易位涉及GLUT4在未受刺激的细胞中穿过的相同隔室之间的重新分布，其中GLUT4从高尔基体和反高尔基体网络隔室显著募集。我们全面的近端蛋白质图谱提供了一个集成的，高密度的，全细胞会计的本地化GLUT4的分辨率为1020 nm，作为一个结构框架，了解调节GLUT4运输下游的不同信号输入在生理相关的细胞类型的分子机制。 摘要：近端蛋白质图谱提供了一个高分辨率，全细胞帐户GLUT4的本地化在未刺激和刺激的人肌肉细胞，揭示了GLUT4的运输调控的结构框架。
Regulation of glucose transport, which is central for control of whole-body metabolism, is determined by the amount of GLUT4 glucose transporter (also known as SLC2A4) in the plasma membrane (PM) of fat and muscle cells. Physiologic signals [such as activated insulin receptor or AMP-activated protein kinase (AMPK)] increase PM GLUT4. Here, we show that the distribution of GLUT4 between the PM and interior of human muscle cells is dynamically maintained, and that AMPK promotes PM redistribution of GLUT4 by regulating exocytosis and endocytosis. Stimulation of exocytosis by AMPK is mediated by Rab10 and the Rab GTPase-activating protein TBC1D4. APEX2 proximity mapping reveals that GLUT4 traverses both PM-proximal and PM-distal compartments in unstimulated muscle cells, further supporting retention of GLUT4 by a constitutive retrieval mechanism. AMPK-stimulated translocation involves GLUT4 redistribution among the same compartments traversed in unstimulated cells, with a significant recruitment of GLUT4 from the Golgi and trans-Golgi network compartments. Our comprehensive proximal protein mapping provides an integrated, high-density, whole-cell accounting of the localization of GLUT4 at a resolution of ∼20 nm that serves as a structural framework for understanding the molecular mechanisms regulating GLUT4 trafficking downstream of different signaling inputs in a physiologically relevant cell type. Summary: Proximal protein mapping provides a high-resolution, whole-cell account of GLUT4 localization in unstimulated and stimulated human muscle cells, revealing the structural framework for regulation of GLUT4 trafficking.
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影响因子：
14.8
作者：
Hung V;Udeshi ND;Lam SS;Loh KH;Cox KJ;Pedram K;Carr SA;Ting AY
通讯作者：
Ting AY
GLUT4储存囊泡的蛋白质组学分析揭示了抑制肿瘤候选者5（TUSC5）是脂肪细胞中胰岛素作用的新调节剂。
DOI：
10.1074/jbc.m115.657361
发表时间：
2015-09-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fazakerley DJ;Naghiloo S;Chaudhuri R;Koumanov F;Burchfield JG;Thomas KC;Krycer JR;Prior MJ;Parker BL;Murrow BA;Stöckli J;Meoli CC;Holman GD;James DE
通讯作者：
James DE
影响因子：
5.3
作者：
Govers, R;Coster, ACF;James, DE
通讯作者：
James, DE
影响因子：
29
作者：
Eguez, L;Lee, A;McGraw, TE
通讯作者：
McGraw, TE
影响因子：
4.8
作者：
Gonzalez-Munoz, Elena;Lopez-Iglesias, Carmen;Camps, Marta
通讯作者：
Camps, Marta