OVEREXPRESSION OF THE NEURAL GROWTH-ASSOCIATED PROTEIN GAP-43 INDUCES NERVE SPROUTING IN THE ADULT NERVOUS-SYSTEM OF TRANSGENIC MICE
OVEREXPRESSION OF THE NEURAL GROWTH-ASSOCIATED PROTEIN GAP-43 INDUCES NERVE SPROUTING IN THE ADULT NERVOUS-SYSTEM OF TRANSGENIC MICE
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DOI：
10.1016/0092-8674(95)90168-x
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发表时间：
1995-10-20
期刊：
影响因子：
64.5
通讯作者：
CARONI, P
中科院分区：
文献类型：
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作者：
AIGNER, L;ARBER, S;CARONI, P
神经突生长和结构可塑性的调节可能涉及控制生长能力的内在决定因素的表达。我们通过将生长相关蛋白 GAP-43 的组成型表达靶向成年转基因小鼠的神经元来测试这个概念。这些小鼠在神经肌肉接头处和海马杂乱纤维的末端区域表现出惊人的自发神经萌芽。在对照小鼠中，这些神经纤维不表达 GAP-43，并且不会自发萌芽。在 GAP-43 过表达的小鼠中，损伤诱导的神经萌芽和神经再支配过程中的末端树枝化大大增强。不能被 PKC 磷酸化的突变体 GAP-43 的促芽活性降低。结果表明 GAP-43 是神经突生长和可塑性的内在突触前决定因素。
Regulation of neurite outgrowth and structural plasticity may involve the expression of intrinsic determinants controlling growth competence. We have tested this concept by targeting constitutive expression of the growth-associated protein GAP-43 to the neurons of adult transgenic mice. Such mice showed striking spontaneous nerve sprouting at the neuromuscular junction and in the terminal field of hippocampal messy fibers. In control mice, these nerve fibers did not express GAP-43, and did not sprout spontaneously. Lesion-induced nerve sprouting and terminal arborization during reinnervation were greatly potentiated in GAP-43-overexpressing mice. A mutant GAP-43 that cannot be phosphorylated by PKC had reduced sprout-promoting activity. The results establish GAP-43 as an intrinsic presynaptic determinant for neurite outgrowth and plasticity.