Protein kinase Cξ mediates insulin-induced glucose transport through actin remodeling in L6 muscle cells
Protein kinase Cξ mediates insulin-induced glucose transport through actin remodeling in L6 muscle cells
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DOI：
10.1091/mbc.e05-10-0969
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Tong, PCY
中科院分区：
文献类型：
--
作者：
Liu, LZ;Zhao, HL;Tong, PCY
蛋白激酶C (PKC) zeta与胰岛素诱导的骨骼肌细胞葡萄糖摄取有关，尽管其潜在机制尚不清楚。在本研究中，我们研究了PKC zeta对表达myc标记的葡萄糖转运蛋白4 （GLUT4）的分化大鼠L6肌细胞中肌动蛋白重塑和葡萄糖转运的影响。在胰岛素刺激下，PKC zeta从低密度微粒体转移到质膜，同时GLUT4易位和葡萄糖摄取增加。z -扫描共聚焦显微镜显示，胰岛素刺激后，重新定位的PKC zeta与小GTPase Rac-1、actin和GLUT4在空间上共定位。wortmannin和细胞渗透性PKC zeta假底物肽抑制胰岛素介导的共定位、PKC zeta分布、GLUT4易位和葡萄糖摄取。在稳定转染的细胞中，PKC zeta的过表达引起肌动蛋白重塑的胰岛素样效应，同时在缺乏胰岛素的情况下，GLUT4易位增加2.1倍，葡萄糖摄取增加1.7倍。细胞渗透性PKC zeta假底物肽可消除PKC zeta过表达的影响，而wortmannin则不能。瞬时转染组成型活性Rac-1可使PKC zeta形成类似肌动蛋白重构的新结构，而显性阴性Rac-1可阻止胰岛素介导的PKC zeta易位。总之，这些结果表明PKC zeta通过肌动蛋白重塑介导胰岛素对葡萄糖转运的影响。
Protein kinase C (PKC) zeta has been implicated in insulin-induced glucose uptake in skeletal muscle cell, although the underlying mechanism remains unknown. In this study, we investigated the effect of PKC zeta on actin remodeling and glucose transport in differentiated rat L6 muscle cells expressing myc-tagged glucose transporter 4 (GLUT4). On insulin stimulation, PKC zeta translocated from low-density microsomes to plasma membrane accompanied by increase in GLUT4 translocation and glucose uptake. Z-scan confocal microscopy revealed a spatial colocalization of relocated PKC zeta with the small GTPase Rac-1, actin, and GLUT4 after insulin stimulation. The insulin-mediated colocalization, PKC zeta distribution, GLUT4 translocation, and glucose uptake were inhibited by wortmannin and cell-permeable PKC zeta pseudosubstrate peptide. In stable transfected cells, overexpression of PKC zeta caused an insulin-like effect on actin remodeling accompanied by a 2.1-fold increase in GLUT4 translocation and 1.7-fold increase in glucose uptake in the absence of insulin. The effects of PKC zeta overexpression were abolished by cell-permeable PKC zeta pseudosubstrate peptide, but not wortmannin. Transient transfection of constitutively active Rac-1 recruited PKC zeta to new structures resembling actin remodeling, whereas dominant negative Rac-1 prevented the insulin-mediated PKC zeta translocation. Together, these results suggest that PKC zeta mediates insulin effect on glucose transport through actin remodeling in muscle cells.