Local sharing as a predominant determinant of synaptic matrix molecular dynamics.

Local sharing as a predominant determinant of synaptic matrix molecular dynamics.
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DOI:
10.1371/journal.pbio.0040271
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发表时间:
2006-09
期刊:
影响因子:
9.8
通讯作者:
Ziv, Noam E
Ziv, Noam E
中科院分区:
生物学1区
文献类型:
--
作者:
Tsuriel, Shlomo;Geva, Ran;Zamorano, Pedro;Dresbach, Thomas;Boeckers, Tobias;Gundelfinger, Eckart D;Garner, Craig C;Ziv, Noam E

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最近的研究表明,中枢神经系统突触可以持续数周、数月,甚至一生,但人们对突触如何长期保持其结构和功能特征知之甚少。作为更好地理解突触维持的一步,我们分别检查了突出的突触前和突触后基质分子 Synapsin I 和 ProSAP2/Shank3 的丢失、重新分配、重新整合和补充动态。光漂白和光活化实验后的荧光恢复表明,这两种分子在几分钟到几小时的时间尺度内不断从突触结构中丢失、重新分布和重新纳入其中。交换率不受抑制蛋白质合成或蛋白酶体介导的蛋白质降解的影响,通过刺激加速,并且大大超过来自体细胞来源的补充率。这些发现表明,关键突触基质分子的动力学可能由局部蛋白质交换和重新分布主导,而蛋白质合成和降解则用于维持和调节这些蛋白质的局部共享池的大小。为了了解突触维持过程,作者检查了两种关键突触蛋白 Synapsin I 和 ProSAP2/Shank3 的丢失、重新分配、重新整合和补充动态。
Recent studies suggest that central nervous system synapses can persist for weeks, months, perhaps lifetimes, yet little is known as to how synapses maintain their structural and functional characteristics for so long. As a step toward a better understanding of synaptic maintenance we examined the loss, redistribution, reincorporation, and replenishment dynamics of Synapsin I and ProSAP2/Shank3, prominent presynaptic and postsynaptic matrix molecules, respectively. Fluorescence recovery after photobleaching and photoactivation experiments revealed that both molecules are continuously lost from, redistributed among, and reincorporated into synaptic structures at time-scales of minutes to hours. Exchange rates were not affected by inhibiting protein synthesis or proteasome-mediated protein degradation, were accelerated by stimulation, and greatly exceeded rates of replenishment from somatic sources. These findings indicate that the dynamics of key synaptic matrix molecules may be dominated by local protein exchange and redistribution, whereas protein synthesis and degradation serve to maintain and regulate the sizes of local, shared pools of these proteins. To understand processes involved in synaptic maintenance, the authors examine the loss, redistribution, reincorporation and replenishment dynamics of two key synaptic proteins, Synapsin I and ProSAP2/Shank3.