神经元细胞骨架与轴突生长的研究进展

ADVANCEMENT OF CYTOSKELETON AND AXON OUTGROWTH OF NEURON

目的总结神经元细胞骨架的结构特点、与轴突生长的关系及细胞内细胞骨架的信号调控机制。方法查阅近年有关神经元细胞骨架与轴突生长的文献,并进行综述。结果神经元主要的细胞骨架微丝与微管具有高度极性与动态性,二者之间存在相互作用。无论是轴突吸引分子还是轴突排斥分子,均是通过膜内传导,最终作用于细胞骨架来实现对神经元轴突生长的影响。改变生长锥内细胞骨架的动态性及它们相互作用的动态性将影响轴突的生长。神经元内的Rho-GTP酶及糖原合成酶激酶3β(glycogen synthase kinase3β,GSK-3β)这两个关键分子主要参与了细胞骨架动态性的调节。结论神经元轴突生长的实质是协调肌动蛋白丝与微管以及它们之间相互作用的动态性和轴突再生。调控Rho-GTP酶及GSK-3β的活性是调控细胞骨架动态性、促进轴突再生的关键。相同的机制也介导了脊髓损伤后的轴突再生。

Objective To summarize the advancement of cytoskeleton and axon outgrowth of neuron. Methods The recent literature concerning cytoskeleton and axon outgrowth of neuron was reviewed and summarized. Results The actin filaments and microtubules in neuron were highly polarized and dynamic structures confined to the tips of axons and the reciprocal interactions between these two major cytoskeletal polymers was also dynamic. Attractive or a repulsive cue whose final common path of action was the growth cone cytoskeleton mediated the growth of axons of neuron by intracellular signaling cascades. Regulating the actin filament and microtubule dynamics as well as their interactions in growth cones played a key role in neurite outgrowth and axon guidance. Rho-GTPases and glycogen synthase kinase 3β （GSK-3β）, the two major intracellular signaling pathways had emerged in recent years as candidates for regulating the dynamics of actin filaments and microtubules. Conclusion The axon outgrowth and guidance depend on well-coordinated cytoskeletal and reciprocal interaction dynamics which also mediate axon regeneration after spinal cord injury. Regulating activity of Rho-GTPases and GSK-3β simultaneously may acts as key role to regulate the dynamics of cytoskeletal and to determine axon outgrowth.