Lipid rafts mediate chemotropic guidance of nerve growth cones
Lipid rafts mediate chemotropic guidance of nerve growth cones
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DOI：
10.1016/s0896-6273(04)00157-6
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发表时间：
2004-04-08
期刊：
影响因子：
16.2
通讯作者：
Zheng, JQ
中科院分区：
文献类型：
--
作者：
Guirland, C;Suzuki, S;Zheng, JQ
轴突的定向运动需要胞外信号通过质膜进行转导。在这里，我们提出证据，胆固醇和鞘脂富集膜微域（脂筏）介导特定的神经生长锥的引导反应。通过针对胆固醇或神经节苷脂的各种方法破坏脂筏，分别选择性地消除BDNF和netrin-1梯度中的生长锥吸引和排斥，而不影响谷氨酸诱导的吸引力。有趣的是，在BDNF或netrin-1中，生长锥一侧的局部木筏断裂产生了与梯度相反的转向响应。筏操作也阻断了信号蛋白3a诱导的生长锥排斥、抑制和塌陷。最后，诱导反应似乎涉及筏依赖的p42/p44 MAPK激活和配体诱导的脂质筏受体募集。结合在生长锥上观察到的不对称受体-筏关联，我们的研究结果表明，通过膜筏的局部信号传导在调节细胞外信号对发育中的轴突的引导作用中起作用。
Axon guidance requires signal transduction of extracellular cues through the plasma membrane for directional motility. Here we present evidence that cholesterol- and sphingolipid-enriched membrane microdomains (lipid rafts) mediate specific guidance responses of nerve growth cones. Disruption of lipid rafts by various approaches targeting cholesterol or gangliosides selectively abolished growth cone attraction and repulsion in BDNF and netrin-1 gradients, respectively, without affecting glumamate-induced attraction. Interestingly, local raft disruption on one side of the growth cone in bath BDNF or netrin-1 produced opposite turning responses to that induced by the gradients. Raft manipulation also blocked Semaphorin 3A-induced growth cone repulsion, inhibition, and collapse. Finally, guidance responses appeared to involve raft-dependent activation of p42/p44 MAPK and ligand-induced receptor recruitment to lipid rafts. Together with the observation of asymmetric receptor-raft associations at the growth cone in guidance gradients, our findings indicate that localized signaling through membrane rafts plays a role in mediating guidance actions of extracellular cues on developing axons.