Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes.
Dual role for myosin II in GLUT4-mediated glucose uptake in 3T3-L1 adipocytes.
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DOI：
10.1016/j.yexcr.2008.08.007
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发表时间：
2008-10-15
影响因子：
3.7
通讯作者：
Patel, Yashomati M.
中科院分区：
文献类型：
--
作者：
Fulcher, F. Kent;Smith, Bethany T.;Russ, Misty;Patel, Yashomati M.
胰岛素刺激的葡萄糖摄取需要激活几种信号通路来介导GLUT 4囊泡向质膜的易位和融合。我们以前的研究表明，GLUT 4介导的葡萄糖摄取是一个肌球蛋白II依赖的过程中的脂肪细胞。本报告中描述的实验是第一个显示肌球蛋白IIA亚型特异性调节胰岛素刺激的脂肪细胞葡萄糖摄取的双重作用。我们证明，MLCK的抑制，但不是RhoK的结果在受损的胰岛素刺激的葡萄糖摄取。此外，我们的研究表明，胰岛素通过MLCK特异性地刺激与肌球蛋白IIA亚型相关的RLC的磷酸化。在时程实验中，我们确定GLUT 4在肌球蛋白IIA募集之前易位到质膜。我们进一步表明，肌球蛋白IIA的质膜招聘需要肌球蛋白IIA被激活通过MLCK的RLC的磷酸化。我们的研究结果还表明，肌球蛋白II是必要的适当GLUT囊泡融合在质膜。我们发现，一旦在质膜，肌球蛋白II参与调节胰岛素刺激后GLUT 4的内在活性。总的来说，我们的研究结果是第一次揭示，肌球蛋白IIA在介导胰岛素刺激的葡萄糖摄取在3 T3-LI脂肪细胞，通过GLUT 4囊泡融合在质膜和GLUT 4活性的关键作用。
Insulin-stimulated glucose uptake requires the activation of several signaling pathways to mediate the translocation and fusion of GLUT4 vesicles to the plasma membrane. Our previous studies demonstrated that GLUT4-mediated glucose uptake is a myosin II-dependent process in adipocytes. The experiments described in this report are the first to show a dual role for the myosin IIA isoform specifically in regulating insulin-stimulated glucose uptake in adipocytes. We demonstrate that inhibition of MLCK but not RhoK results in impaired insulin-stimulated glucose uptake. Furthermore, our studies show that insulin specifically stimulates the phosphorylation of the RLC associated with the myosin IIA isoform via MLCK. In time course experiments, we determined that GLUT4 translocates to the plasma membrane prior to myosin IIA recruitment. We further show that recruitment of myosin IIA to the plasma membrane requires that myosin IIA be activated via phosphorylation of the RLC by MLCK. Our findings also reveal that myosin II is required for proper GLUT-vesicle fusion at the plasma membrane. We show that once at the plasma membrane, myosin II is involved in regulating the intrinsic activity of GLUT4 after insulin stimulation. Collectively, our results are the first to reveal that myosin IIA plays a critical role in mediating insulin-stimulated glucose uptake in 3T3-LI adipocytes, via both GLUT4 vesicle fusion at the plasma membrane and GLUT4 activity.
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