Zhao Y, Szaro B G
Department of Biological Sciences and the Neurobiology Research Center, University at Albany, State University of New York, 12222, USA.
J Neurobiol. 1997 Nov 20;33(6):811-24.
Neurofilaments are an important structural component of the axonal cytoskeleton and are made of neuronal intermediate filament (nIF) proteins. During axonal development, neurofilaments undergo progressive changes in molecular composition. In mammals, for example, highly phosphorylated forms of the middle- and high-molecular-weight neurofilament proteins (NF-M and NF-H, respectively) are characteristic of mature axons, whereas nIF proteins such as alpha-internexin are typical of young axons. Such changes have been proposed to help growing axons accommodate varying demands for plasticity and stability by modulating the structure of the axonal cytoskeleton. Xefiltin is a recently discovered nIF protein of the frog Xenopus laevis, whose nervous system has a large capacity for regeneration and plasticity. By amino acid identity, xefiltin is closely related to two other nIF proteins, alpha-internexin and gefiltin. alpha-Internexin is found principally in embryonic axons of the mammalian brain, and gefiltin is expressed primarily in goldfish retinal ganglion cells and has been associated with the ability of the goldfish optic nerve to regenerate. Like gefiltin in goldfish, xefiltin in Xenopus is the most abundantly expressed nIF protein of mature retinal ganglion cells. In the present study, we used immunocytochemistry to study the distribution of xefiltin during optic nerve development and regeneration. During development, xefiltin was found in optic axons at stage 35/36, before they reach the tectum at stage 37/38. Similarly, after an orbital crush injury, xefiltin first reemerged in optic axons after the front of regeneration reached the optic chiasm, but before it reached the tectum. Thus, during both development and regeneration, xefiltin was present within actively growing optic axons. In addition, aberrantly projecting retinoretinal axons expressed less xefiltin than those entering the optic tract, suggesting that xefiltin expression is influenced by interactions between regenerating axons and cells encountered along the visual pathway. These results support the idea that changes in xefiltin expression, along with those of other nIF proteins, modulate the structure and stability of actively growing optic axons and that this stability is under the control of the pathway which growing axons follow.
神经丝是轴突细胞骨架的重要结构成分，由神经元中间丝（nIF）蛋白组成。在轴突发育过程中，神经丝的分子组成会发生渐进性变化。例如，在哺乳动物中，中分子量和高分子量神经丝蛋白（分别为NF-M和NF-H）的高度磷酸化形式是成熟轴突的特征，而诸如α-中间丝蛋白等nIF蛋白则是幼嫩轴突的典型代表。有人提出，这种变化有助于生长中的轴突通过调节轴突细胞骨架的结构来适应对可塑性和稳定性的不同需求。Xefiltin是最近在非洲爪蟾（Xenopus laevis）中发现的一种nIF蛋白，其神经系统具有很强的再生和可塑性能力。从氨基酸同源性来看，Xefiltin与另外两种nIF蛋白α-中间丝蛋白和gefiltin密切相关。α-中间丝蛋白主要存在于哺乳动物脑的胚胎轴突中，而gefiltin主要在金鱼视网膜神经节细胞中表达，并与金鱼视神经的再生能力有关。与金鱼中的gefiltin一样，爪蟾中的Xefiltin是成熟视网膜神经节细胞中表达最丰富的nIF蛋白。在本研究中，我们使用免疫细胞化学方法研究了Xefiltin在视神经发育和再生过程中的分布。在发育过程中，在35/36期的视神经轴突中发现了Xefiltin，此时轴突在37/38期到达视顶盖之前。同样，在眼眶挤压损伤后，Xefiltin在再生前沿到达视交叉但尚未到达视顶盖之前首次重新出现在视神经轴突中。因此，在发育和再生过程中，Xefiltin都存在于活跃生长的视神经轴突中。此外，异常投射的视网膜视网膜轴突比进入视束的轴突表达的Xefiltin少，这表明Xefiltin的表达受再生轴突与视觉通路中遇到的细胞之间相互作用的影响。这些结果支持这样一种观点，即Xefiltin表达的变化以及其他nIF蛋白的变化调节活跃生长的视神经轴突的结构和稳定性，并且这种稳定性受生长轴突所遵循的通路的控制。
