A novel actin cytoskeleton-dependent noncaveolar microdomain composed of homo-oligomeric caveolin-2 for activation of insulin signaling
A novel actin cytoskeleton-dependent noncaveolar microdomain composed of homo-oligomeric caveolin-2 for activation of insulin signaling
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DOI：
10.1016/j.bbamcr.2013.05.003
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发表时间：
2013-10-01
影响因子：
5.1
通讯作者：
Pak, Yunbae
中科院分区：
文献类型：
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作者：
Kwon, Hayeong;Lee, Jaewoong;Pak, Yunbae
小窝蛋白-2（cav-2）的作用，独立于小窝蛋白-1（cav-1）和小窝，仍然难以捉摸。我们的数据表明，cav-2存在于质膜（PM）在细胞缺乏cav-1和形成同源寡聚体复合物。Cav-2与cavin-1和cavin-2在PM中不相互作用。Rab 6-GTP是必需的微管依赖性的cav-2从高尔基体到PM独立的cav-1的胞吐运输。cav-2-寡聚化的noncaveolar微结构域不受胆固醇消耗的影响，并免受二氧化硅包被的PM的剪切。胰岛素受体（IR）的激活在微区进行。肌动蛋白解聚影响cav-2-寡聚化noncaveolar微结构域的形成和维持，并减弱IR向微结构域的募集，从而抑制IR信号的激活。Cav-2 shRNA稳定细胞和异位表达寡聚化结构域截短突变体Cav-2（Delta 47-86）的细胞表现出通过非小窝微结构域的IR信号激活的延迟。cav-2表达状态的升高使得cav-1下调或/和胆固醇耗尽的细胞中IR信号的非小窝激活。我们的研究结果揭示了一种新的同源寡聚cav-2微结构域负责调节PM中IR信号的激活。(C)2013爱思唯尔有限公司版权所有。
The role of caveolin-2 (cav-2), independently of caveolin-1 (cav-1) and caveolae, has remained elusive. Our data show that cav-2 exists in the plasma membrane (PM) in cells lacking cav-1 and forms homo-oligomeric complexes. Cav-2 did not interact with cavin-1 and cavin-2 in the PM. Rab6-GTP was required for the microtubule-dependent exocytic transport of cav-2 from the Golgi to the PM independently of cav-1. The cav-2-oligomerized noncaveolar microdomain was unaffected by cholesterol depletion and protected from shearing of silica-coated PM. Activation of insulin receptor (IR) was processed in the microdomain. Actin depolymerization affected the formation and sustenance of cav-2-oligomerized noncaveolar microdomain and attenuated IR recruitment to the microdomain thereby inhibiting IR signaling activation. Cav-2 shRNA stable cells and the cells ectopically expressing an oligomerization domain truncation mutant, cav-2(Delta 47-86) exhibited retardation of IR signaling activation via the noncaveolar microdomain. Elevation in status of cav-2 expression rendered the noncaveolar activation of IR signaling in cav-1 down-regulated or/and cholesterol-depleted cells. Our findings reveal a novel homo-oligomeric cav-2 microdomain responsible for regulating activation of IR signaling in the PM. (C) 2013 Elsevier B.V. All rights reserved.