Bi-directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity
Bi-directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity
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DOI：
10.1111/j.1460-9568.2005.04510.x
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发表时间：
2005-12-01
影响因子：
3.4
通讯作者：
Okabe, S
中科院分区：
文献类型：
--
作者：
Iki, J;Inoue, A;Okabe, S
Cordyn是一种F-肌动蛋白相关蛋白，其在SH 3结构域与突触后支架蛋白Shank相互作用，并定位于小鼠神经元的树突棘内。绿色荧光蛋白（GFP）为基础的时间推移成像显示皮质蛋白从树突细胞质的突触后位点的应用脑源性神经营养因子（BDNF）的重新分布。这种反应是由丝裂原活化蛋白（MAP）激酶激活介导的，并依赖于C-末端SH 3结构域。与此相反，N-甲基-D-天冬氨酸（NMDA）受体的激活引起的损失corneum从突触后位点。这种NMDA依赖的再分布被Src家族激酶抑制剂阻断。相反，增加Src家族激酶活性诱导皮质素磷酸化和皮质素从突触后位点的损失。最后，内源性BDNF的阻断减少了突触后位点的皮质素的量，而NMDA受体拮抗剂阻止了这种减少。这些结果表明，在神经元发育过程中，BDNF和NMDA受体介导的信号转导在突触后肌动蛋白细胞骨架重组中的平衡的重要性。
Cortactin is an F-actin-associated protein which interacts with the postsynaptic scaffolding protein Shank at the SH3 domain and is localized within the dendritic spine in the mouse neuron. Green fluorescent protein (GFP)-based time-lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain-derived neurotrophic factor (BDNF). This response was mediated by mitogen-activated protein (MAP) kinase activation and was dependent on the C-terminal SH3 domain. In contrast, activation of N-methyl-D-aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. This NMDA-dependent redistribution was blocked by an Src family kinase inhibitor. Conversely, increasing Src family kinase activity induced cortactin phosphorylation and loss of cortactin from the postsynaptic sites. Finally, blocking of endogenous BDNF reduced the amount of cortactin at the postsynaptic sites and an NMDA receptor antagonist prevented this reduction. These results indicate the importance of counterbalance between BDNF and NMDA receptor-mediated signalling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.