Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes
Sortilin is essential and sufficient for the formation of Glut4 storage vesicles in 3T3-L1 adipocytes
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DOI：
10.1016/j.devcel.2005.04.004
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发表时间：
2005-07-01
影响因子：
11.8
通讯作者：
Kandror, KV
中科院分区：
文献类型：
--
作者：
Shi, J;Kandror, KV
在脂肪和骨骼肌细胞中，葡萄糖转运蛋白亚型4（Glut 4）向质膜的易位受损可能代表2型糖尿病发展中的主要缺陷。Glut 4定位于专门的储存囊泡（GSV）中，其生物学性质和生物发生尚不清楚。在这里，我们报告说，GSV形成分化的3 T3-L1脂肪细胞后，分拣蛋白诱导分化的第2天。在分拣蛋白诱导之前Glut 4的强制表达导致转运蛋白的快速降解，而分拣蛋白的过表达增加GSV的形成并刺激胰岛素调节的葡萄糖摄取。敲低分拣蛋白可降低GSV的形成和胰岛素调节的葡萄糖摄取。最后，我们通过Glut 4和分拣蛋白的双重转染在未分化细胞中重建了功能性GSV。因此，分拣蛋白不仅是必需的，而且对于GSV的生物发生和脂肪细胞中胰岛素反应性的获得是足够的。
Impaired translocation of the glucose transporter isoform 4 (Glut4) to the plasma membrane in fat and skeletal muscle cells may represent a primary defect in the development of type 2 diabetes mellitus. Glut4 is localized in specialized storage vesicles (GSVs), the biological nature and blogenesis of which are not known. Here, we report that GSVs are formed in differentiating 3T3-L1 adipocytes upon induction of sortilin on day 2 of differentiation. Forced expression of Glut4 prior to induction of sortilin leads to rapid degradation of the transporter, whereas overexpression of sortilin increases formation of GSVs and stimulates insulin-regulated glucose uptake. Knockdown of sortilin decreases both formation of GSVs and insulin-regulated glucose uptake. Finally, we have reconstituted functional GSVs in undifferentiated cells by double transfection of Glut4 and sortilin. Thus, sortilin is not only essential, but also sufficient for biogenesis of GSVs and acquisition of insulin responsiveness in adipose cells.