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首页> 外文期刊>Cell motility and the cytoskeleton >Control of neurite outgrowth and growth cone motility by phosphatidylinositol-3-kinase.
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Control of neurite outgrowth and growth cone motility by phosphatidylinositol-3-kinase.

机译：通过磷脂酰肌醇-3-激酶控制神经突的生长和生长锥的运动。

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摘要

Phosphatidylinositol-3-kinase (PI-3K) has been reported to affect neurite outgrowth both in vivo and in vitro. Here we investigated the signaling pathways by which PI-3K affects neurite outgrowth and growth cone motility in identified snail neurons in vitro. Inhibition of PI-3K with wortmannin (2 microM) or LY 294002 (25 microM) resulted in a significant elongation of filopodia and in a slow-down of neurite outgrowth. Experiments using cytochalasin and blebbistatin, drugs that interfere with actin polymerization and myosin II activity, respectively, demonstrated that filopodial elongation resulting from PI-3K inhibition was dependent on actin polymerization. Inhibition of strategic kinases located downstream of PI-3K, such as Akt, ROCK, and MEK, also caused significant filopodial elongation and a slow-down in neurite outgrowth. Another growth cone parameter, filopodial number, was not affected by inhibition of PI-3K, Akt, ROCK, or MEK. A detailed study of growth cone behavior showed that the filopodialelongation induced by inhibiting PI-3K, Akt, ROCK, and MEK was achieved by increasing two motility parameters: the rate with which filopodia extend (extension rate) and the time that filopodia spend elongating. Whereas the inhibition of ROCK or Akt (both activated by the lipid kinase activity of PI-3K) and MEK (activated by the protein kinase activity of PI-3K) had additive effects, simultaneous inhibition of Akt and ROCK showed no additive effect. We further demonstrate that the effects on filopodial dynamics investigated were calcium-independent. Taken together, our results suggest that inhibition of PI-3K signaling results in filopodial elongation and a slow-down of neurite advance, reminiscent of growth cone searching behavior.
机译：据报道，磷脂酰肌醇-3-激酶（PI-3K）在体内和体外均可影响神经突生长。在这里，我们调查了PI-3K在体外识别的蜗牛神经元中影响神经突生长和生长锥运动的信号传导途径。用渥曼青霉素（2 microM）或LY 294002（25 microM）抑制PI-3K会导致丝状伪足的显着延长和神经突增生的减慢。使用细胞松弛素和blebbistatin分别干扰肌动蛋白聚合和肌球蛋白II活性的药物进行的实验表明，由PI-3K抑制引起的丝状延伸取决于肌动蛋白聚合。位于PI-3K下游的战略激酶（如Akt，ROCK和MEK）的抑制作用也引起显着的丝状延伸和神经突增生的减慢。 PI-3K，Akt，ROCK或MEK的抑制作用不影响另一个生长锥参数fi虫数。对生长锥行为的详细研究表明，抑制PI-3K，Akt，ROCK和MEK诱导的丝状双伸长是通过增加两个运动参数来实现的：丝状伪足的延伸速率（延伸速率）和丝状伪足的伸长时间。尽管对ROCK或Akt（均由PI-3K的脂质激酶活性激活）和MEK（由PI-3K的蛋白激酶活性激活）的抑制具有累加作用，但同时抑制Akt和ROCK却没有显示累加作用。我们进一步证明，对所研究的丝虫动态的影响是不依赖钙的。两者合计，我们的结果表明，PI-3K信号的抑制导致丝状体伸长和神经突推进减慢，令人联想到生长锥搜索行为。

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