Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD-95
Activity-independent regulation of dendrite patterning by postsynaptic density protein PSD-95
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DOI：
10.1523/jneurosci.2379-06.2006
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发表时间：
2006-10-04
影响因子：
5.3
通讯作者：
Firestein, Bonnie L.
中科院分区：
文献类型：
--
作者：
Charych, Erik I.;Akum, Barbara F.;Firestein, Bonnie L.
树突的形态决定了神经元功能的许多方面，包括动作电位的传播和信息处理。然而，问题仍然是如何建立不同的神经元树突分支模式。在这里，我们报告说，突触后密度-95（PSD-95），参与树突棘成熟和突触信号蛋白的聚类蛋白，在调节树突生长和分支，独立于其突触功能发挥着新的作用。在未成熟的神经元中，PSD-95的过度表达降低了经历额外分支的初级树突的比例，导致次级树突数量的显著减少。相反，在未成熟神经元中敲低PSD-95蛋白增加次级树突数量。PSD-95的作用是活性独立的，并被cypin拮抗，cypin是一种调节PSD-95定位的非突触蛋白。cypin与PSD-95的结合与稳定树突分支的形成相关。最后，PSD-95在COS-7细胞中的过表达破坏了微管组织，表明PSD-95可以调节微管以调节树突状分支。尽管已经确定了许多调节树突数量的因素，但我们的研究结果提供了直接证据，表明主要参与突触功能的蛋白质也可以在塑造神经元树突分支模式方面发挥发育作用。
Dendritic morphology determines many aspects of neuronal function, including action potential propagation and information processing. However, the question remains as to how distinct neuronal dendrite branching patterns are established. Here, we report that postsynaptic density-95 (PSD-95), a protein involved in dendritic spine maturation and clustering of synaptic signaling proteins, plays a novel role in regulating dendrite outgrowth and branching, independent of its synaptic functions. In immature neurons, overexpression of PSD-95 decreases the proportion of primary dendrites that undergo additional branching, resulting in a marked reduction of secondary dendrite number. Conversely, knocking down PSD-95 protein in immature neurons increases secondary dendrite number. The effect of PSD-95 is activity-independent and is antagonized by cypin, a nonsynaptic protein that regulates PSD-95 localization. Binding of cypin to PSD-95 correlates with formation of stable dendrite branches. Finally, overexpression of PSD-95 in COS-7 cells disrupts microtubule organization, indicating that PSD-95 may modulate microtubules to regulate dendritic branching. Whereas many factors have been identified which regulate dendrite number, our findings provide direct evidence that proteins primarily involved in synaptic functions can also play developmental roles in shaping how a neuron patterns its dendrite branches.