Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation
Chemotropic responses of retinal growth cones mediated by rapid local protein synthesis and degradation
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DOI：
10.1016/s0896-6273(01)00551-7
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发表时间：
2001-12-26
期刊：
影响因子：
16.2
通讯作者：
Holt, CE
中科院分区：
文献类型：
--
作者：
Campbell, DS;Holt, CE
生长锥包含mRNA，翻译机器，以及我们在这里报告的蛋白质降解机器。我们发现，孤立的视网膜生长锥立即失去了他们的能力，把netrin-1或Sema 3A的趋化梯度时，翻译被抑制。翻译抑制还防止Sema 3A诱导的塌陷，而LPA诱导的塌陷不受影响。蛋白酶体功能的抑制阻断对netrin-1和LPA的应答，但不影响Sema 3A应答。我们进一步证明，在分离的生长锥，netrin-1和Sema 3A激活翻译起始因子，并刺激显着上升的蛋白质合成在几分钟内，而netrin-1和LPA引起类似的上升泛素-蛋白质结合物。这些结果表明，引导分子通过触发生长锥中蛋白质水平的快速局部变化来引导轴突生长。
Growth cones contain mRNAs, translation machinery, and, as we report here, protein degradation machinery. We show that isolated retinal growth cones immediately lose their ability to turn in a chemotropic gradient of netrin-1 or Sema3A when translation is inhibited. Translation inhibition also prevents Sema3A-induced collapse, while LPA-induced collapse is not affected. Inhibition of proteasome function blocks responses to netrin-1 and LPA but does not affect Sema3A responses. We further demonstrate in isolated growth cones that netrin-1 and Sema3A activate translation initiation factors and stimulate a marked rise in protein synthesis within minutes, while netrin-1 and LPA elicit similar rises in ubiquitin-protein conjugates. These results suggest that guidance molecules steer axon growth by triggering rapid local changes in protein levels in growth cones.