A role for kinesin in insulin-stimulated GLUT4 glucose transporter translocation in 3T3-L1 adipocytes
A role for kinesin in insulin-stimulated GLUT4 glucose transporter translocation in 3T3-L1 adipocytes
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DOI：
10.1074/jbc.m010785200
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发表时间：
2001-04-06
影响因子：
4.8
通讯作者：
Czech, MP
中科院分区：
文献类型：
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作者：
Emoto, M;Langille, SE;Czech, MP
胰岛素通过刺激隔离的葡萄糖转运蛋白4 （GLUT4）从细胞膜到细胞表面的运动来调节脂肪细胞和肌肉的葡萄糖摄取。在这里，我们报道胰岛素介导的最佳GLUT4易位依赖于培养脂肪细胞中的微管和基于肌动蛋白的细胞骨架结构，3T3-L1脂肪细胞中微管和f -肌动蛋白的解聚导致核周含GLUT4膜的分散，并消除胰岛素对GLUT4向质膜移动的作用。此外，在3T3-L1脂肪细胞中外源表达的微管结合蛋白hTau40，会损害向微管正端移动的运动蛋白马达，显著延迟胰岛素反应时质膜上GLUT4的出现。在这些条件下，hTau40蛋白对微管结构或核周GLUT4定位没有可检测到的影响。这些结果与肌动蛋白和基于微管的细胞骨架以及运动蛋白马达的假设一致，这些假设指导GLUT4易位到质膜以响应胰岛素。
Insulin regulates glucose uptake in adipocytes and muscle by stimulating the movement of sequestered glucose transporter 4 (GLUT4) proteins from intracellular membranes to the cell surface. Here we report that optimal insulin-mediated GLUT4 translocation is dependent upon both microtubule and actin-based cytoskeletal structures in cultured adipocytes, Depolymerization of microtubules and F-actin in 3T3-L1 adipocytes causes the dispersion of perinuclear GLUT4-containing membranes and abolishes insulin action on GLUT4 movements to the plasma membrane. Furthermore, heterologous expression in 3T3-L1 adipocytes of the microtubule-binding protein hTau40, which impairs kinesin motors that move toward the plus ends of microtubules, markedly delayed the appearance of GLUT4 at the plasma membrane in response to insulin, The hTau40 protein had no detectable effect on microtubule structure or perinuclear GLUT4 localization under these conditions. These results are consistent with the hypothesis that both the actin and microtubule-based cytoskeleton, as well as a kinesin motor, direct the translocation of GLUT4 to the plasma membrane in response to insulin.