A preformed complex of postsynaptic proteins is involved in excitatory synapse development

A preformed complex of postsynaptic proteins is involved in excitatory synapse development
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DOI:
10.1016/j.neuron.2006.01.015
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发表时间:
2006-02-16
期刊:
影响因子:
16.2
通讯作者:
El-Husseini, A
El-Husseini, A
中科院分区:
医学1区
文献类型:
--
作者:
Gerrow, K;Romorini, S;El-Husseini, A

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非突触簇的突触后蛋白质已被记录,然而,他们的作用仍然难以捉摸。当支架蛋白的非突触簇最丰富时,我们监测了与突触发生有关的几种候选蛋白的运输。我们发现了一种蛋白质复合物,它由两种在含量、流动性和参与突触形成方面不同的蛋白质组成。一个亚群是移动的,并依赖于肌动蛋白运输交付新生和现有的突触。这些移动的簇包含支架蛋白PSD-95、GKAP和Shank。表现出缓慢运动和短距离行进的一部分移动的簇包含神经配素-1。第二组由固定的非突触支架复合物组成,主要含有神经连接素-1,可以招募含有突触素的轴突运输囊泡,并容易转化为功能性突触前接触,回收活体染料FM 4-64。这些结果假定了一种机制,即预先形成的支架蛋白复合物作为预先确定的突触后热点建立新的功能兴奋性突触。
Nonsynaptic clusters of postsynaptic proteins have been documented; however, their role remains elusive. We monitored the trafficking of several candidate proteins implicated in synaptogenesis, when nonsynaptic clusters of scaffold proteins are most abundant. We find a protein complex consisting of two populations that differ in their content, mobility, and involvement in synapse formation. One subpopulation is mobile and relies on actin transport for delivery to nascent and existing synapses. These mobile clusters contain the scaffolding proteins PSD-95, GKAP, and Shank. A proportion of mobile clusters that exhibits slow movement and travels short distances contains neuroligin-1. The second group consists of stationary nonsynaptic scaffold complexes that mainly contain neuroligin-1, can recruit synaptophysin-containing axonal transport vesicles, and are readily transformed to functional presynaptic contacts that recycle the vital dye FM 4-64. These results postulate a mechanism whereby preformed scaffold protein complexes serve as predetermined postsynaptic hotspots for establishment of new functional excitatory synapses.