Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathway
Unconventional myosin Myo1c promotes membrane fusion in a regulated exocytic pathway
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DOI：
10.1128/mcb.24.12.5447-5458.2004
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发表时间：
2004-06-01
影响因子：
5.3
通讯作者：
Czech, MP
中科院分区：
文献类型：
--
作者：
Bose, A;Robida, S;Czech, MP
葡萄糖稳态部分通过调节肌肉和脂肪组织的葡萄糖摄取来控制。含有 GLUT4 葡萄糖转运蛋白的细胞内膜囊泡响应胰岛素向细胞皮层移动，然后与质膜融合。在这里，我们表明融合步骤因磷脂酰肌醇 (PI) 3-激酶的抑制而延迟。用 PI 3 激酶抑制剂 LY294002 处理胰岛素刺激的 3T3-L1 脂肪细胞会导致含有 GLUT4 的囊泡在细胞表面下方积聚。融合前含有 GLUT4 的囊泡在质膜附近的积累需要完整的细胞骨架网络和非常规的肌球蛋白运动 Myo1c。值得注意的是，在这些条件下增强的 Myo1c 表达会导致广泛的膜波纹，并克服 LY294002 引起的膜融合阻断，恢复 GLUT4 在细胞外部的显示。超快显微镜分析表明，胰岛素治疗导致含有 GLUT4 的囊泡动员到 Myo1c 诱导的膜褶皱的这些区域。因此，Myo1c 马达驱动的局部膜重塑似乎促进了含有 GLUT4 的胞吐囊泡与脂肪细胞质膜的融合。
Glucose homeostasis is controlled in part by regulation of glucose uptake into muscle and adipose tissue. Intracellular membrane vesicles containing the GLUT4 glucose transporter move towards the cell cortex in response to insulin and then fuse with the plasma membrane. Here we show that the fusion step is retarded by the inhibition of phosphatidylinositol (PI) 3-kinase. Treatment of insulin-stimulated 3T3-L1 adipocytes with the PI 3-kinase inhibitor LY294002 causes the accumulation of GLUT4-containing vesicles just beneath the cell surface. This accumulation of GLUT4-containing vesicles near the plasma membrane prior to fusion requires an intact cytoskeletal network and the unconventional myosin motor Myo1c. Remarkably, enhanced Myo1c expression under these conditions causes extensive membrane ruffling and overrides the block in membrane fusion caused by LY294002, restoring the display of GLUT4 on the cell exterior. Ultrafast microscopic analysis revealed that insulin treatment leads to the mobilization of GLUT4-containing vesicles to these regions of Myo1c-induced membrane ruffles. Thus, localized membrane remodeling driven by the Myo1c motor appears to facilitate the fusion of exocytic GLUT4-containing vesicles with the adipocyte plasma membrane.