Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking
Ins (endocytosis) and outs (exocytosis) of GLUT4 trafficking
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DOI：
10.1016/j.ceb.2007.04.018
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发表时间：
2007-08-01
影响因子：
7.5
通讯作者：
Pessin, Jeffrey E.
中科院分区：
文献类型：
--
作者：
Hou, June Chunqiu;Pessin, Jeffrey E.
葡萄糖转运蛋白4（glucose transporter 4，GLUT 4）是胰岛素调节的主要葡萄糖转运蛋白，主要表达于肌肉和脂肪组织。GLUT 4储存在特征不明确的细胞内囊泡区室中，并响应胰岛素刺激而易位至细胞表面，导致葡萄糖摄取增加。这一过程对于维持正常的葡萄糖稳态是必不可少的，并且涉及运输事件和细胞内信号级联的复杂相互作用。最近的研究已经确定分拣蛋白是脂肪形成过程中形成GLUT 4储存囊泡的必要元素，高尔基体定位的含γ-耳的Arf结合蛋白（GGA）是新合成的GLUT 4进入专门的隔室的关键外壳适配器。胰岛素刺激的GLUT 4从该隔室转运至质膜似乎需要称为AS 160的Akt/蛋白激酶B底物（160 kDa的Akt底物）。此外，含有VPS 9结构域的蛋白Gapex-5与CIP 4复合似乎起到Rab 31鸟嘌呤核苷酸交换因子的作用，这是胰岛素刺激的GLUT 4易位所必需的。本文就GLUT 4囊泡的生物发生、胞内运输和膜融合等方面的研究进展作一综述。
Glucose transporter 4 (GLUT4) is the major insulin-regulated glucose transporter expressed mainly in muscle and adipose tissue. GLUT4 is stored in a poorly characterized intracellular vesicular compartment and translocates to the cell surface in response to insulin stimulation resulting in an increased glucose uptake. This process is essential for the maintenance of normal glucose homeostasis and involves a complex interplay of trafficking events and intracellular signaling cascades. Recent studies have identified sortilin as an essential element for the formation of GLUT4 storage vesicles during adipogenesis and Golgi-localized gamma-ear-containing Arf-binding protein (GGA) as a key coat adaptor for the entry of newly synthesized GLUT4 into the specialized compartment. Insulin-stimulated GLUT4 translocation from this compartment to the plasma membrane appears to require the Akt/protein kinase B substrate termed AS160 (Akt substrate of 160 kDa). In addition, the VPS9 domain-containing protein Gapex-5 in complex with CIP4 appears to function as a Rab31 guanyInucleotide exchange factor that is necessary for insulin-stimulated GLUT4 translocation. Here, we attempt to summarize recent advances in GLUT4 vesicle biogenesis, intracellular trafficking and membrane fusion.