The actin cross-linking protein AFAP120 regulates axon elongation in a tyrosine phosphorylation-dependent manner.

The actin cross-linking protein AFAP120 regulates axon elongation in a tyrosine phosphorylation-dependent manner.
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DOI:
10.1016/j.neulet.2008.08.036
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发表时间:
2008-10-24
影响因子:
2.5
通讯作者:
Lanier LM
Lanier LM
中科院分区:
医学4区
文献类型:
--
作者:
Harder J;Xu X;Letourneau P;Lanier LM

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生长锥引导和轴突延长需要肌动蛋白细胞骨架的动态协调调节。随着生长锥的移动,肌动蛋白依赖的力量产生张力,使外周的突出活动成为可能,并驱动生长锥移位。肌动蛋白细胞骨架的这种动态重塑响应于膜张力,需要激活Src激酶。尽管有人提出,这些肌动蛋白依赖的力量随着肌动蛋白交联度的不同而不同,但交联蛋白(S)的身份仍然不清楚。AFAP120是一种神经系统特异性肌动蛋白交联蛋白,受Src激酶磷酸化调控。在这里,我们报告了AFAP120在分化的小脑颗粒细胞中表达和酪氨酸磷酸化,在那里它在轴突和生长锥中丰富。AFAP120的过表达以酪氨酸磷酸化依赖的方式促进轴突的延长。这些发现表明,AFAP120可能使Src信号与肌动蛋白细胞骨架的动态变化相协调,从而驱动生长锥运动和轴突延长。
Growth cone guidance and axon elongation require the dynamic coordinated regulation of the actin cytoskeleton. As the growth cone moves, actin-dependent forces generate tension that enables protrusive activity in the periphery and drives growth cone translocation. This dynamic remodeling of the actin cytoskeleton in response to membrane tension requires activation of Src kinase. Although it has been proposed that these actin-dependent forces vary with the extent of actin cross-linking, the identity of the cross-linking protein(s) remains unknown. AFAP120 is a nervous system specific actin cross-linking protein that is regulated by Src kinase phosphorylation. Here, we report that AFAP120 is expressed and tyrosine phosphorylated in differentiating cerebellar granule cells, where it is enriched in the axon and growth cone. Over-expression of AFAP120 enhances neurite elongation in a tyrosine phosphorylation dependent manner. These findings suggest that AFAP120 may coordinate Src signaling with the dynamic changes in the actin cytoskeleton that drive growth cone motility and axon elongation.
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