CHANGES IN CYTOSKELETAL PROTEIN-SYNTHESIS FOLLOWING AXON INJURY AND DURING AXON REGENERATION
CHANGES IN CYTOSKELETAL PROTEIN-SYNTHESIS FOLLOWING AXON INJURY AND DURING AXON REGENERATION
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DOI：
10.1007/bf02780547
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发表时间：
1992-06-01
影响因子：
5.1
通讯作者：
TETZLAFF, W
中科院分区：
文献类型：
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作者：
BISBY, MA;TETZLAFF, W
面运动神经元轴突损伤刺激肌动蛋白、微管蛋白和GAP-43的合成增加，神经丝蛋白的合成减少：mRNA水平相应变化。与外周神经元对轴突切断的强烈反应相反，受损的中枢神经系统神经元表现出减弱的反应，随后中止（红核脊髓神经元）或细胞骨架蛋白mRNA表达的总体降低有证据表明，这些合成变化受多种因素调节，包括神经内或靶源性营养因子的丧失，损伤部位产生的阳性信号，轴突内蛋白质周转的变化，以及胶质细胞产生的因子对靶源性营养支持的替代。结论是，目前还没有一致的解释上调或下调的任何细胞骨架蛋白后，轴突切断或在regeneration.In考虑的相关性，这些变化在细胞骨架蛋白合成的再生，它强调，他们不太可能参与最初的生长受损轴突，既因为过境时间之间的细胞体和损伤部位太长，因为发芽可以发生在孤立的轴突中。损伤诱导的微管蛋白和肌动蛋白在近端轴突中的轴突运输的加速可能在提供初始轴突生长所需的细胞骨架蛋白方面更重要。随后，增加的肌动蛋白和微管蛋白的合成和运输速度增加了这些蛋白质的递送，以支持成熟再生轴突的体积增加。神经丝合成的减少和神经丝磷酸化的改变可能使其他细胞骨架蛋白的转运速度增加，很少有直接证据表明细胞骨架蛋白合成的改变是成功再生所必需的，在缺乏支持性环境的情况下也是不够的。然而，一个强大的细胞体反应和成功的再生之间存在的相关性表明，轴突损伤后的细胞骨架蛋白合成的调节的理解必须是任何成功的策略，以提高中枢神经系统的再生能力的一部分。
Injury to the axons of facial motoneurons stimulates increases in the synthesis of actin, tubulins, and GAP-43, and decreases in the synthesis of neurofilament proteins: mRNA levels change correspondingly. In contrast to this robust response of peripheral neurons to axotomy, injured central nervous system neurons show either an attenuated response that is subsequently aborted (rubrospinal neurons) or overall decreases in cytoskeletal protein mRNA expression (corticospinal and retinal ganglion neurons).There is evidence that these changes in synthesis are regulated by a variety of factors, including loss of endoneurially or target-derived trophic factors, positive signals arising from the site of injury, changes in the intraaxonal turnover of proteins, and substitution of target-derived trophic support by factors produced by glial cells. It is concluded that there is, as yet, no coherent explanation for the upregulation or downregulation of any of the cytoskeletal proteins following axotomy or during regeneration.In considering the relevance of these changes in cytoskeletal protein synthesis to regeneration, it is emphasized that they are unlikely to be involved in the initial outgrowth of the injured axons, both because transit times between cell body and injury site are too long, and because sprouting can occur in isolated axons. Injury-induced acceleration of the axonal transport of tubulin and actin in the proximal axon is likely to be more important in providing the cytoskeletal protein required for initial axonal outgrowth. Subsequently, the increased synthesis and transport velocity for actin and tubulin increase the delivery of these proteins to support the increased volume of the maturing regenerating axons. Reduction in neurofilament synthesis and changes in neurofilament phosphorylation may permit the increased transport velocity of the other cytoskeletal proteins.There is little direct evidence that alterations in cytoskeletal protein synthesis are necessary for successful regeneration, nor are they sufficient in the absence of a supportive environment. Nevertheless, the correlation that exists between a robust cell body response and successful regeneration suggests that an understanding of the regulation of cytoskeletal protein synthesis following axon injury must be a part of any successful strategy to improve the regenerative capacity of the central nervous system.