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Glucose transporter recycling in response to insulin is facilitated by myosin Myo1c

机译:肌球蛋白Myo1c促进响应胰岛素的葡萄糖转运蛋白循环

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Insulin stimulates glucose uptake in muscle and adipocytes by signalling the translocation of GLUT4 glucose transporters from intracellular membranes to the cell surface. The translocation of GLUT4 may involve signalling pathways that are both independent of and dependent on phosphatidylinositol-3-OH kinase (PI(3)K). This translocation also requires the actin cytoskele-ton, and the rapid movement of GLUT4 along linear tracks may be mediated by molecular motors. Here we report that the unconventional myosin Myolc is present in GLUT4-containing vesicles purified from 3T3-L1 adipocytes. Myolc, which contains a motor domain, three IQ motifs and a carboxy-terminal cargo domain, is highly expressed in primary and cultured adipocytes. Insulin enhances the localization of Myolc with GLUT4 in cortical tubulovesicular structures associated with actin filaments, and this colocalization is insensitive to wortmannin. Insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane is augmented by the expression of wild-type Myolc and inhibited by a dominant-negative cargo domain of Myolc. A decrease in the expression of endogenous Myolc mediated by small interfering RNAs inhibits insulin-stimulated uptake of 2-deoxyglucose. Thus, myosin Myolc functions in a PI(3)K-independent insulin signalling pathway that controls the movement of intracellular GLUT4-containing vesicles to the plasma membrane.
机译:胰岛素通过信号传递GLUT4葡萄糖转运蛋白从细胞内膜到细胞表面的转运来刺激肌肉和脂肪细胞中的葡萄糖吸收。 GLUT4的易位可能涉及独立于并依赖于磷脂酰肌醇-3-OH激酶(PI(3)K)的信号通路。这种易位也需要肌动蛋白的细胞骨架,并且GLUT4沿着线性轨迹的快速运动可能是由分子马达介导的。在这里,我们报告非常规的肌球蛋白Myolc存在于从3T3-L1脂肪细胞纯化的含GLUT4的囊泡中。 Myolc包含一个运动域,三个IQ模式和一个羧基末端货物域,在原代和培养的脂肪细胞中高度表达。胰岛素增强与肌动蛋白丝相关的皮层肾小管结构中带有GLUT4的Myolc的定位,这种共定位对渥曼青霉素不敏感。胰岛素刺激的GLUT4向脂肪细胞质膜的转运通过野生型Myolc的表达增强,并被Myolc的显性负货物域抑制。小干扰RNA介导的内源性Myolc表达的减少会抑制胰岛素刺激的2-脱氧葡萄糖摄取。因此,肌球蛋白Myolc在独立于PI(3)K的胰岛素信号通路中起作用,该通路控制细胞内含GLUT4的囊泡向质膜的运动。

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