Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions
Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions
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DOI：
10.1073/pnas.93.8.3679
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发表时间：
1996-04-16
影响因子：
11.1
通讯作者：
Czernik, AJ
中科院分区：
文献类型：
--
作者：
Jovanovic, JN;Benfenati, F;Czernik, AJ
神经营养因子调节神经元群体存活和分化的能力涉及Trk/MAP最近，神经营养因子也被证明调节突触传递。突触蛋白是神经元特异性磷蛋白家族，其在调节神经递质释放、轴突伸长以及突触接触的形成和维持中发挥作用，我们在这里报告，突触蛋白I是神经营养因子/Trk/MAP激酶级联的下游效应器，使用纯化的组分，我们表明MAP激酶在三个位点（Ser-62，Ser-67和Ser-549）化学计量磷酸化突触蛋白I。在大鼠脑匀浆、培养的皮层神经元和分离的突触前末梢中检测到这些位点的磷酸化。脑源性神经营养因子和神经生长因子分别上调完整皮层神经元和PC 12细胞中MAP激酶依赖位点的突触蛋白I磷酸化，而KCl诱导的培养神经元去极化降低了这些位点的磷酸化状态。MAP激酶依赖的突触蛋白I磷酸化显著降低了其促进G-肌动蛋白聚合和捆绑肌动蛋白丝的能力。结果表明，MAP激酶依赖的突触蛋白I磷酸化可能有助于神经营养因子和其他信号通路在MAP激酶激活水平上对突触可塑性的调节。
The ability of neurotrophins to modulate the survival and differentiation of neuronal populations involves the Trk/MAP (mitogen-activated protein kinase) kinase signaling pathway, More recently, neurotrophins have also been shown to regulate synaptic transmission, The synapsins are a family of neuron-specific phosphoproteins that play a role in regulation of neurotransmitter release, in axonal elongation, and in formation and maintenance of synaptic contacts, We report here that synapsin I is a downstream effector for the neurotrophin/Trk/MAP kinase cascade, Using purified components, we show that MAP kinase stoichiometrically phosphorylated synapsin I at three sites (Ser-62, Ser-67, and Ser-549). Phosphorylation of these sites was detected in rat brain homogenates, in cultured cerebrocortical neurons, and in isolated presynaptic terminals, Brain-derived neurotrophic factor and nerve growth factor upregulated phosphorylation of synapsin I at MAP kinase-dependent sites in intact cerebrocortical neurons and PC12 cells, respectively, while KCI-induced depolarization of cultured neurons decreased the phosphorylation state at these sites, MAP kinase-dependent phosphorylation of synapsin I significantly reduced its ability to promote G-actin polymerization and to bundle actin filaments, The results suggest that MAP kinase-dependent phosphorylation of synapsin I may contribute to the modulation of synaptic plasticity by neurotrophins and by other signaling pathways that converge at the level of MAP kinase activation.