Brain-derived neurotrophic factor regulation of retinal growth cone filopodial dynamics is mediated through actin depolymerizing factor/cofilin
Brain-derived neurotrophic factor regulation of retinal growth cone filopodial dynamics is mediated through actin depolymerizing factor/cofilin
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DOI：
10.1523/jneurosci.2836-04.2004
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发表时间：
2004-11-24
影响因子：
5.3
通讯作者：
Letourneau, PC
中科院分区：
文献类型：
--
作者：
Gehler, S;Shaw, AE;Letourneau, PC
神经营养因子调节生长锥运动的分子机制尚不清楚。本研究探讨了参与转导BDNF诱导的丝状伪足动力学增加的信号转导。我们的研究结果表明，BDNF调节丝状伪足的长度和数量通过Rho激酶依赖的机制。此外，肌动蛋白解聚因子（ADF）/cofilin活性是必要的，足以抵消BDNF的作用。我们的数据表明，ADF/cofilin的激活模拟BDNF对丝状伪足动力学的影响，而ADF/cofilin的不活动则阻断了BDNF的影响。此外，BDNF通过减少ADF/cofilin的磷酸化来促进ADF/cofilin的活化。虽然肌球蛋白II的抑制也增强丝状伪足的长度，我们的研究结果表明，BDNF信号是独立的肌球蛋白II的活性和这两个途径的结果在累加效应丝状伪足长度。因此，丝状伪足的延伸至少由两种独立的机制调节。BDNF依赖性途径通过调节ADF/cofilin起作用，独立于肌球蛋白II活性。
The molecular mechanisms by which neurotrophins regulate growth cone motility are not well understood. This study investigated the signaling involved in transducing BDNF-induced increases of filopodial dynamics. Our results indicate that BDNF regulates filopodial length and number through a Rho kinase-dependent mechanism. Additionally, actin depolymerizing factor (ADF)/cofilin activity is necessary and sufficient to transduce the effects of BDNF. Our data indicate that activation of ADF/cofilin mimics the effects of BDNF on filopodial dynamics, whereas ADF/cofilin inactivity blocks the effects of BDNF. Furthermore, BDNF promotes the activation of ADF/cofilin by reducing the phosphorylation of ADF/cofilin. Although inhibition of myosin II also enhances filopodial length, our results indicate that BDNF signaling is independent of myosin II activity and that the two pathways result in additive effects on filopodial length. Thus, filopodial extension is regulated by at least two independent mechanisms. The BDNF-dependent pathway works via regulation of ADF/cofilin, independently of myosin II activity.