Zhang Xiao-Feng, Schaefer Andrew W, Burnette Dylan T, Schoonderwoert Vincent T, Forscher Paul
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Neuron. 2003 Dec 4;40(5):931-44. doi: 10.1016/s0896-6273(03)00754-2.
Rho family GTPases have been implicated in neuronal growth cone guidance; however, the underlying cytoskeletal mechanisms are unclear. We have used multimode fluorescent speckle microscopy (FSM) to directly address this problem. We report that actin arcs that form in the transition zone are incorporated into central actin bundles in the C domain. These actin structures are Rho/Rho Kinase (ROCK) effectors. Specifically, LPA mediates growth cone retraction by ROCK-dependent increases in actin arc and central actin bundle contractility and stability. In addition, these treatments had marked effects on MT organization as a consequence of strong MT-actin arc interactions. In contrast, LPA or constitutively active Rho had no effect on P domain retrograde actin flow or filopodium bundle number. This study reveals a novel mechanism for domain-specific spatial control of actin-based motility in the growth cone with implications for understanding chemorepellant growth cone responses and nerve regeneration.
Rho家族GTP酶与神经元生长锥导向有关；然而，其潜在的细胞骨架机制尚不清楚。我们使用多模式荧光斑点显微镜（FSM）来直接解决这个问题。我们报告称，在过渡区形成的肌动蛋白弧被整合到C结构域的中央肌动蛋白束中。这些肌动蛋白结构是Rho/ Rho激酶（ROCK）效应器。具体而言，溶血磷脂酸（LPA）通过依赖ROCK的肌动蛋白弧和中央肌动蛋白束收缩性及稳定性增加来介导生长锥回缩。此外，由于强烈的微管（MT）-肌动蛋白弧相互作用，这些处理对MT组织有显著影响。相比之下，LPA或组成型活性Rho对P结构域逆行肌动蛋白流或丝状伪足束数量没有影响。这项研究揭示了一种在生长锥中基于肌动蛋白的运动进行结构域特异性空间控制的新机制，这对于理解化学排斥性生长锥反应和神经再生具有重要意义。
