A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth
A protein kinase A-dependent molecular switch in synapsins regulates neurite outgrowth
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DOI：
10.1038/nn840
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发表时间：
2002-05-01
影响因子：
25
通讯作者：
Greengard, P
中科院分区：
文献类型：
--
作者：
Kao, HT;Song, HJ;Greengard, P
环磷酸腺苷（cAMP）通过激活蛋白激酶A（PKA）促进多种神经元细胞系中的轴突生长。我们用非洲爪蟾胚胎神经元培养和完整的X. laevis胚胎，cAMP/PKA的神经生长促进作用部分介导的突触蛋白在一个单一的氨基酸残基的磷酸化。表达突变形式的突触蛋白，防止磷酸化在这个网站上，或引入磷酸特异性抗体针对这个网站，减少基础和二丁酰cAMP刺激的神经突生长。在基础条件下和PKA抑制剂存在下，在该位点模拟组成性磷酸化的突变的表达增加了神经突的生长。这些结果提供了一个潜在的刺激神经元再生的分子方法，损伤后和神经退行性疾病。
Cyclic AMP (cAMP) promotes neurite outgrowth in a variety of neuronal cell lines through the activation of protein kinase A (PKA). We show here, using both Xenopus laevis embryonic neuronal culture and intact X. laevis embryos, that the nerve growth-promoting action of cAMP/PKA is mediated in part by the phosphorylation of synapsins at a single amino acid residue. Expression of a mutated form of synapsin that prevents phosphorylation at this site, or introduction of phospho-specific antibodies directed against this site, decreased basal and dibutyryl cAMP-stimulated neurite outgrowth. Expression of a mutation mimicking constitutive phosphorylation at this site increased neurite outgrowth, both under basal conditions and in the presence of a PKA inhibitor. These results provide a potential molecular approach for stimulating neuron regeneration, after injury and in neuro-degenerative diseases.