Lipid rafts and integrin activation regulate oligodendrocyte survival
Lipid rafts and integrin activation regulate oligodendrocyte survival
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DOI：
10.1523/jneurosci.5725-03.2004
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发表时间：
2004-04-14
影响因子：
5.3
通讯作者：
ffrench-Constant, C
中科院分区：
文献类型：
--
作者：
Decker, L;ffrench-Constant, C
中枢神经系统中新形成的少突胶质细胞从其靶轴突获得生存信号。这些信号部分由轴突上表达的层粘连蛋白提供，层粘连蛋白被少突胶质细胞上的α 6 β 1整联蛋白识别，并通过磷脂酰肌醇3 '-激酶（PI 3 K）途径放大血小板衍生生长因子（PDGF）信号传导。α 6 β 1整联蛋白定位于少突胶质细胞脂筏中。我们在这里使用鞘脂合成抑制剂伏马菌素-B1耗尽筏，这种定位是重要的正常生存信号，因为耗尽增加少突胶质细胞凋亡和抑制PI 3 K信号。我们以前已经表明，PDGF介导的整合素激活是少突胶质细胞增殖信号的重要组成部分，在这里，我们提出的证据表明，一个类似的机制在生存信号。使用锰的整合素活化增加筏定位并挽救筏耗尽和PDGF去除对存活和PI 3 K信号传导的影响。总之，这些结果表明，筏在少突胶质细胞生存信号的基础上提供了一个有利的环境生长因子介导的整合素激活的重要作用。
Newly formed oligodendrocytes in the CNS derive survival cues from their target axons. These cues are provided in part by laminins expressed on the axon, which are recognized by alpha6beta1 integrin on the oligdendrocyte and amplify platelet-derived growth factor (PDGF) signaling through the phosphatidylinositol 3'-kinase (PI3K) pathway. The alpha6beta1 integrin is localized in oligodendrocyte lipid rafts. We show here using the sphingolipid synthesis inhibitor fumonisin-B1 to deplete rafts that this localization is important for normal survival signaling, because depletion increases oligodendrocyte apoptosis and inhibits PI3K signaling. We have shown previously that PDGF-mediated integrin activation is an important component of oligodendrocyte proliferation signaling, and here we present evidence that a similar mechanism operates in survival signaling. Integrin activation using manganese increases raft localization and rescues the effects of both raft depletion and PDGF removal on survival and PI3K signaling. Together, these results point to an essential role for rafts in oligodendrocyte survival signaling on the basis of the provision of a favorable environment for growth factor-mediated integrin activation.