Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction
Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction
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DOI：
10.1074/jbc.m211785200
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发表时间：
2003-03-28
影响因子：
4.8
通讯作者：
Liao, K
中科院分区：
文献类型：
--
作者：
Huo, HR;Guo, XM;Liao, K
脂筏/小窝被发现是必不可少的胰岛素样生长因子（IGF）-1受体信号在3 T3-L1前脂肪细胞分化诱导。在3 T3-L1细胞中，IGF-1受体位于质膜的脂筏/小窝中，并可直接与小窝中的主要蛋白组分小窝蛋白-1相互作用。通过使用胆固醇结合试剂β-甲基环糊精或菲律宾肽消耗细胞胆固醇来破坏脂筏/小窝，从而阻断3 T3-L1前脂肪细胞中的IGF-1受体信号传导。激素诱导的脂肪细胞分化和有丝分裂克隆扩增均受到脂筏/小窝破坏的抑制。然而，非特异性脂质结合试剂甲苯噻嗪不影响脂肪细胞分化或有丝分裂克隆扩增。进一步的研究表明，脂筏/小窝仅是IGF-1受体下游信号传导所需的，而不是配体激活受体本身所需的。因此，我们的研究结果表明，在脂筏/小窝的定位和与小窝蛋白的协会使IGF-1受体有密切的联系，下游信号分子招募到脂筏/小窝，并通过这些信号分子复合物传递信号。
Lipid rafts/caveolae are found to be essential for insulin-like growth factor (IGF)-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction. In 3T3-L1 cells, IGF-1 receptor is located in lipid rafts/caveolae of the plasma membrane and can directly interact with caveolin-1, the major protein component in caveolae. Disruption of lipid rafts/caveolae by depleting cellular cholesterol with cholesterol-binding reagent, beta-methylcyclodextrin or filipin, blocks the IGF-1 receptor signaling in 3T3-L1 preadipocyte. Both hormonal induced adipocyte differentiation and mitotic clonal expansion are inhibited by lipid rafts/caveolae disruption. However, a nonspecific lipid binding reagent, xylazine, does not affect adipocyte differentiation or mitotic clonal expansion. Further studies indicate that lipid rafts/caveolae are required only for IGF-1 receptor downstream signaling and not the activation of receptor itself by ligand. Thus, our results suggest that localization in lipid rafts/caveolae and association with caveolin enable IGF-1 receptor to have a close contact with downstream signal molecules recruited into lipid rafts/caveolae and transmit the signal through these signal molecule complexes.