A proteolytic pathway that controls glucose uptake in fat and muscle.
A proteolytic pathway that controls glucose uptake in fat and muscle.
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DOI：
10.1007/s11154-013-9276-2
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发表时间：
2014-03
影响因子：
8.2
通讯作者：
Bogan JS
中科院分区：
文献类型：
--
作者：
Belman JP;Habtemichael EN;Bogan JS
胰岛素通过控制GLUT4葡萄糖转运体的亚细胞位置来调节葡萄糖摄取。在低胰岛素状态下，GLUT4被隔离在脂肪和肌肉细胞内，并在胰岛素刺激下转移到细胞表面。TUG蛋白是一种功能性系链，将GLUT4隔离在高尔基体基质中。为了刺激葡萄糖摄取，胰岛素触发了TRAG内切蛋白的分解。在胰岛素将GLUT4动员到细胞表面的急性作用中，裂解作用占很大比例。在持续的胰岛素暴露中，内吞的GLUT4直接从内小体循环到质膜，并绕过了TRAG调节的运输步骤。胰岛素通过TC10αGTP酶及其效应蛋白PIST刺激TRAG切割。这一作用通过AS160/TBC1D4和Tbc1D1与胰岛素信号协调，以调节Rab GTP酶，并与其他信号协调以指导整体GLUT4靶向。数据支持这样的观点，即N-末端TUG切割产物TUGUL作为一种新型的泛素样蛋白修饰剂，促进GLUT4移动到细胞表面。C-末端的TRAG裂解产物是从高尔基体基质中提取出来的，它腾出了一个“锚定”位置，允许随后的GLUT4保留和释放循环。总之，GLUT4囊泡易位和TRAG裂解可能与含有GLUT4的囊泡中存在的其他蛋白质的生理效应以及TUG C末端产物的潜在额外效应相协调。了解这一GLUT4滞留和释放的TRAG通路将有助于阐明葡萄糖摄取的调节和2型糖尿病的发病机制。
Insulin regulates glucose uptake by controlling the subcellular location of GLUT4 glucose transporters. GLUT4 is sequestered within fat and muscle cells during low-insulin states, and is translocated to the cell surface upon insulin stimulation. The TUG protein is a functional tether that sequesters GLUT4 at the Golgi matrix. To stimulate glucose uptake, insulin triggers TUG endoproteolytic cleavage. Cleavage accounts for a large proportion of the acute effect of insulin to mobilize GLUT4 to the cell surface. During ongoing insulin exposure, endocytosed GLUT4 recycles to the plasma membrane directly from endosomes, and bypasses a TUG-regulated trafficking step. Insulin acts through the TC10α GTPase and its effector protein, PIST, to stimulate TUG cleavage. This action is coordinated with insulin signals through AS160/Tbc1D4 and Tbc1D1 to modulate Rab GTPases, and with other signals to direct overall GLUT4 targeting. Data support the idea that the N-terminal TUG cleavage product, TUGUL, functions as a novel ubiquitin-like protein modifier to facilitate GLUT4 movement to the cell surface. The C-terminal TUG cleavage product is extracted from the Golgi matrix, which vacates an “anchoring” site to permit subsequent cycles of GLUT4 retention and release. Together, GLUT4 vesicle translocation and TUG cleavage may coordinate glucose uptake with physiologic effects of other proteins present in the GLUT4-containing vesicles, and with potential additional effects of the TUG C-terminal product. Understanding this TUG pathway for GLUT4 retention and release will shed light on the regulation of glucose uptake and the pathogenesis of type 2 diabetes.
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DOI：
10.1083/jcb.201106098
发表时间：
2011-12-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bruns C;McCaffery JM;Curwin AJ;Duran JM;Malhotra V
通讯作者：
Malhotra V
Rab10 和肌球蛋白-Va 介导脂肪细胞中胰岛素刺激的 GLUT4 储存囊泡易位
DOI：
10.1083/jcb.201111091
发表时间：
2012-08-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chen Y;Wang Y;Zhang J;Deng Y;Jiang L;Song E;Wu XS;Hammer JA;Xu T;Lippincott-Schwartz J
通讯作者：
Lippincott-Schwartz J
影响因子：
4.8
作者：
Bogan, Jonathan S.;Rubin, Bradley R.;Cresswell, James A.
通讯作者：
Cresswell, James A.
影响因子：
4.5
作者：
Cloutier P;Lavallée-Adam M;Faubert D;Blanchette M;Coulombe B
通讯作者：
Coulombe B
影响因子：
4.8
作者：
Chen, J;Wu, A;Baserga, R
通讯作者：
Baserga, R