Src and cortactin promote lamellipodia protrusion and filopodia formation and stability in growth cones.
Src and cortactin promote lamellipodia protrusion and filopodia formation and stability in growth cones.
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DOI：
10.1091/mbc.e15-03-0142
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发表时间：
2015-09-15
影响因子：
3.3
通讯作者：
Suter DM
中科院分区：
文献类型：
--
作者：
He Y;Ren Y;Wu B;Decourt B;Lee AC;Taylor A;Suter DM
Src酪氨酸激酶和corpine如何控制神经生长锥中的肌动蛋白组织和动力学尚不清楚。使用多种高分辨率成像技术，这项研究表明，Src和corneum控制的持久性板状伪足突起以及丝状伪足的形成，稳定性和伸长生长锥。Src酪氨酸激酶与轴突生长和导向有关，然而，其潜在的细胞机制尚不清楚。具体而言，目前还不清楚哪些方面的肌动蛋白的组织和动力学的神经生长锥Src的调节。在这里，我们研究了Src2和它的底物之一，corneum，在板状伪足和丝状伪足的生长锥。我们发现，上调Src2激活状态或corpine增加板状伪足的长度，突出时间，和肌动蛋白网络密度，而下调有相反的效果。此外，Src2或corneum上调增加丝状伪足的密度，长度和突出时间，而下调促进丝状伪足的横向运动。荧光散斑显微镜显示，肌动蛋白组装和逆行流动的速度在任何情况下都没有受到影响。总之，我们的研究结果支持了一个模型，其中Src和corneum调节生长锥运动通过增加肌动蛋白网络密度和突起持久性的板状伪足通过控制肌动蛋白驱动的突起与收缩的状态。此外，这两种蛋白质促进丝状伪足中肌动蛋白束的形成和稳定性。
How Src tyrosine kinase and cortactin control actin organization and dynamics in neuronal growth cones is not well understood. Using multiple high-resolution imaging techniques, this study shows that Src and cortactin control the persistence of lamellipodial protrusion as well as the formation, stability, and elongation of filopodia in growth cones. Src tyrosine kinases have been implicated in axonal growth and guidance; however, the underlying cellular mechanisms are not well understood. Specifically, it is unclear which aspects of actin organization and dynamics are regulated by Src in neuronal growth cones. Here, we investigated the function of Src2 and one of its substrates, cortactin, in lamellipodia and filopodia of Aplysia growth cones. We found that up-regulation of Src2 activation state or cortactin increased lamellipodial length, protrusion time, and actin network density, whereas down-regulation had opposite effects. Furthermore, Src2 or cortactin up-regulation increased filopodial density, length, and protrusion time, whereas down-regulation promoted lateral movements of filopodia. Fluorescent speckle microscopy revealed that rates of actin assembly and retrograde flow were not affected in either case. In summary, our results support a model in which Src and cortactin regulate growth cone motility by increasing actin network density and protrusion persistence of lamellipodia by controlling the state of actin-driven protrusion versus retraction. In addition, both proteins promote the formation and stability of actin bundles in filopodia.