G-protein-coupled receptor cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1-phosphate.
G-protein-coupled receptor cell signaling pathways mediating embryonic chick retinal growth cone collapse induced by lysophosphatidic acid and sphingosine-1-phosphate.
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DOI：
10.1159/000364858
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发表时间：
2014
影响因子：
2.9
通讯作者：
Birgbauer E
中科院分区：
文献类型：
--
作者：
Fincher J;Whiteneck C;Birgbauer E
在神经系统的发育过程中，轴突的正确导航是神经系统的关键问题之一，即轴突导航问题。我们使用小鸡视觉系统作为模型来研究溶血磷脂溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1P）作为潜在轴突引导线索的作用。我们发现LPA和S1P在鸡模型系统中引起特异性的、剂量依赖性的视网膜神经元生长锥塌陷，与小鼠有轻微差异，但与非洲爪蟾非常相似。由于LPA和S1P受体是gpcr，我们使用药物抑制剂分析了鸡视网膜神经元的细胞内信号通路。阻断rho激酶（ROCK）对LPA和S1P对生长锥塌陷有抑制作用，而阻断PLC和螯合钙对生长锥塌陷无影响。百日咳毒素抑制Gi/o导致LPA和S1P部分减少生长锥塌陷。抑制p38可阻断LPA介导的生长锥塌陷，而对S1P不起作用。由此可见，LPA和S1P诱导的鸡视网膜生长锥塌陷除了参与G12/13-ROCK通路外，还部分需要Gi/o。
In the development of the nervous system, one of the critical aspects is the proper navigation of axons to their targets, the problem of axonal guidance. We are using the chick visual system as a model to investigate the role of the lysophospholipids lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) as potential axon guidance cues. We show that both LPA and S1P cause specific, dose-dependent growth cone collapse of retinal neurons in vitro in the chick model system, with slight differences to mouse, but very similar to Xenopus. Because LPA and S1P receptors are GPCRs, we analyzed the intracellular signaling pathways using pharmacological inhibitors in chick retinal neurons. Blocking rho kinase (ROCK) prevented growth cone collapse by LPA and S1P, while blocking PLC or chelating calcium had no effect on growth cone collapse. Inhibiting Gi/o with pertussis toxin resulted in a partial reduction of growth cone collapse, both with LPA and S1P. Inhibition of p38 blocked growth cone collapse mediated by LPA but not S1P. Thus, in addition to the involvement of the G12/13-ROCK pathway, LPA and S1P induced collapse of chick retinal growth cones has a partial requirement for Gi/o.
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