Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems.
Axonally transported proteins associated with axon growth in rabbit central and peripheral nervous systems.
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DOI：
10.1083/jcb.89.1.96
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发表时间：
1981-04
影响因子：
7.8
通讯作者：
Willard, M
中科院分区：
文献类型：
--
作者：
Skene, J H;Willard, M
为了确定神经元的“生长状态”和“成熟状态”是否由不同的基因表达程序区分，我们比较了兔子生长和非生长轴突中的快速运输（I组）蛋白。我们观察到两种多肽（GAP-23和GAP-43），这是特别感兴趣的，因为它们与轴突生长的明显关联。GAP-43在新生动物的中枢神经系统（CNS）（视网膜神经节细胞）轴突中快速转运，但其相对量随着随后的发育而急剧下降。它不能通过成人视神经的轴突切断术重新诱导，所述轴突切断术不再生;然而，它在成人外周神经系统神经（舌下神经，其确实再生）的轴突切断术后诱导，所述轴突切断术前仅运输非常低水平的GAP-43。第二个多肽，GAP-23遵循相同的模式的生长相关的运输，除了它是在未受伤的成年舌下神经运输的显着水平，而不是进一步诱导轴突切断。这些观察结果与“GAP假说”一致，即神经元生长状态可以被定义为基因表达的改变程序，部分由GAP基因的表达所例示，GAP基因的表达产物参与关键的生长特异性功能。当根据GAP假说解释时，它们导致以下结论：（a）生长状态可以被细分为以GAP-23而不是GAP-43的转运为特征的“突触发生状态”，以及需要两个GAP的“轴突伸长状态”;（B）关于GAP基因的表达，再生涉及神经元的新生状态的重演;和（c）哺乳动物CNS神经元不能表达差距基因可能是轴突损伤后CNS轴突不能再生的基础。
In an effort to determine whether the “growth state” and the “mature state” of a neuron are differentiated by different programs of gene expression, we have compared the rapidly transported (group I) proteins in growing and nongrowing axons in rabbits. We observed two polypeptides (GAP-23 and GAP-43) which were of particular interest because of their apparent association with axon growth. GAP-43 was rapidly transported in the central nervous system (CNS) (retinal ganglion cell) axons of neonatal animals, but its relative amount declined precipitously with subsequent development. It could not be reinduced by axotomy of the adult optic nerves, which do not regenerate; however, it was induced after axotomy of an adult peripheral nervous system nerve (the hypoglossal nerve, which does regenerate) which transported only very low levels of GAP-43 before axotomy. The second polypeptide, GAP-23 followed the same pattern of growth-associated transport, except that it was transported at significant levels in uninjured adult hypoglossal nerves and not further induced by axotomy. These observations are consistent with the “GAP hypothesis” that the neuronal growth state can be defined as an altered program of gene expression exemplified in part by the expression of GAP genes whose products are involved in critical growth-specific functions. When interpreted in terms of GAP hypothesis, they lead to the following conclusions: (a) the growth state can be subdivided into a “synaptogenic state” characterized by the transport of GAP-23 but not GAP-43, and an “axon elongation state” requiring both GAPs; (b) with respect to the expression of GAP genes, regeneration involves a recapitulation of a neonatal state of the neuron; and (c) the failure of mammalian CNS neurons to express the GAP genes may underly the failure of CNS axons to regenerate after axon injury.