Cortactin colocalizes with filopodial actin and accumulates at IgCAM adhesion sites in Aplysia growth cones.

Cortactin colocalizes with filopodial actin and accumulates at IgCAM adhesion sites in Aplysia growth cones.
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DOI:
10.1002/jnr.21937
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发表时间:
2009-04
影响因子:
4.2
通讯作者:
Suter, Daniel M.
Suter, Daniel M.
中科院分区:
医学3区
文献类型:
--
作者:
Decourt, Boris;Munnamalai, Vidhya;Lee, Aih Cheun;Sanchez, Lauren;Suter, Daniel M.

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IgCAM和肌动蛋白细胞骨架在神经元生长锥运动和引导中起关键作用。然而,目前还不清楚IgCAM受体如何从质膜传递信号以诱导肌动蛋白重塑。以前的研究表明,局部集群和固定的apCAM,Aapasia同系物的NCAM,诱导Src激酶活性和F-肌动蛋白聚合的外周域培养的Aapasia袋细胞生长锥。因此,我们想测试是否Src激酶底物和肌动蛋白调节剂cornein可以在apCAM介导的生长锥引导过程中Src活性和肌动蛋白组装之间的分子联系。在这里,我们克隆了Aesthesia coronum,并表明它在神经系统中很丰富。生长锥的免疫组化显示,在丝状伪足束和板状伪足的前缘,coronarin与F-肌动蛋白有很强的共定位。细胞骨架的扰动表明,corneum分布在很大程度上取决于肌动蛋白丝。此外,活性Src共定位于肌动蛋白组装的区域,包括前缘和丝状伪足尖端与coronin。最后,我们观察到,corneum,像F-肌动蛋白,本地化的apCAM粘附网站介导的生长锥的指导。总而言之,这些数据表明,coronin是一个中介的IgCAM触发肌动蛋白组装在生长锥和参与运动和指导。
Both IgCAMs and the actin cytoskeleton play critical roles in neuronal growth cone motility and guidance. However, it is unclear how IgCAM receptors transduce signals from the plasma membrane to induce actin remodeling. Previous studies have shown that local clustering and immobilization of apCAM, the Aplysia homolog of NCAM, induces Src kinase activity and F-actin polymerization in the peripheral domain of cultured Aplysia bag cell growth cones. Therefore, we wanted to test whether the Src kinase substrate and actin regulator cortactin could be a molecular link between Src activity and actin assembly during apCAM-mediated growth cone guidance. Here, we cloned Aplysia cortactin and showed that it is abundant in the nervous system. Immunostaining of growth cones revealed a strong colocalization of cortactin with F-actin in filopodial bundles and at the leading edge of lamellipodia. Perturbation of the cytoskeleton indicated that cortactin distribution largely depends on actin filaments. Furthermore, active Src colocalized with cortactin in regions of actin assembly, including leading edge and filopodia tips. Finally, we observed that cortactin, like F-actin, localizes to apCAM adhesion sites mediating growth cone guidance. Altogether, these data suggest that cortactin is a mediator of IgCAM-triggered actin assembly in the growth cone and involved in motility and guidance.
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