Cytoskeleton Protein EB3 Contributes to Dendritic Spines Enlargement and Enhances Their Resilience to Toxic Effects of Beta-Amyloid.
Cytoskeleton Protein EB3 Contributes to Dendritic Spines Enlargement and Enhances Their Resilience to Toxic Effects of Beta-Amyloid.
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DOI：
10.3390/ijms23042274
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发表时间：
2022-02-18
影响因子：
5.6
通讯作者：
Bezprozvanny I
中科院分区：
文献类型：
--
作者：
Pchitskaya E;Rakovskaya A;Chigray M;Bezprozvanny I
EB3蛋白在神经系统中大量表达，并短暂进入正在生长的微管尖端的树突棘，从而导致树突棘增大。然而，动态微管，特别是 EB3 蛋白，在突触功能中的作用仍然难以捉摸。通过控制 EB3 表达水平，我们发现该蛋白是正常树突发生所必需的。尽管如此，EB3 过度表达也会减少海马神经元树突分支和树突总长度。这种效应的发生可能是由于从树突生长到树突棘形成的步骤的神经元发育周期加快。通过对树突棘进行直接形态测量表征，我们发现 EB3 过度表达会导致树突棘头部面积急剧增加。 EB3敲除相反地减少了脊柱头部面积并增加了脊柱颈长度和脊柱颈/脊柱长度比。在模拟阿尔茨海默病的淀粉样蛋白毒性条件下也观察到了相同的效果。颈部伸长被认为是对脊柱形状的常见有害影响，这使得它们在生化和电学上与树突的连接较少。 EB3 还增强突触前蛋白 Synapsin 簇的形成，并且 CaMKII-α 优先定位在海马神经元的棘中而不是树突中，而其下调则具有相反的作用，并减小了突触前蛋白簇 Synapsin 和 PSD95 的大小。 EB3在脊柱发育和成熟中的作用决定了其神经保护作用。 EB3 过度表达使树突棘能够抵抗淀粉样蛋白 - β 的毒性，恢复改变的 PSD95 聚类，并减少在这种病理状态下观察到的树突棘中的 CaMKII-α 定位。
EB3 protein is expressed abundantly in the nervous system and transiently enters the dendritic spines at the tip of the growing microtubule, which leads to spine enlargement. Nevertheless, the role of dynamic microtubules, and particularly EB3 protein, in synapse function is still elusive. By manipulating the EB3 expression level, we have shown that this protein is required for a normal dendritogenesis. Nonetheless, EB3 overexpression also reduces hippocampal neurons dendritic branching and total dendritic length. This effect likely occurs due to the speeding neuronal development cycle from dendrite outgrowth to the step when dendritic spines are forming. Implementing direct morphometric characterization of dendritic spines, we showed that EB3 overexpression leads to a dramatic increase in the dendritic spine head area. EB3 knockout oppositely reduces spine head area and increases spine neck length and spine neck/spine length ratio. The same effect is observed in conditions of amyloid-beta toxicity, modeling Alzheimer`s disease. Neck elongation is supposed to be a common detrimental effect on the spine’s shape, which makes them biochemically and electrically less connected to the dendrite. EB3 also potentiates the formation of presynaptic protein Synapsin clusters and CaMKII-alpha preferential localization in spines rather than in dendrites of hippocampal neurons, while its downregulation has an opposite effect and reduces the size of presynaptic protein clusters Synapsin and PSD95. EB3′s role in spine development and maturation determines its neuroprotective effect. EB3 overexpression makes dendritic spines resilient to amyloid-beta toxicity, restores altered PSD95 clustering, and reduces CaMKII-alpha localization in spines observed in this pathological state.
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影响因子：
16.2
作者：
Berry KP;Nedivi E
通讯作者：
Nedivi E
影响因子：
5.3
作者：
Hu, Xindao;Viesselmann, Chris;Dent, Erik W.
通讯作者：
Dent, Erik W.
DOI：
10.1073/pnas.1517045112
发表时间：
2015-12-15
影响因子：
11.1
作者：
Chen, Xiaobing;Levy, Jonathan M.;Reese, Thomas S.
通讯作者：
Reese, Thomas S.
影响因子：
4.8
作者：
Delgado, Jary Y.;Nall, Duncan;Selvin, Paul R.
通讯作者：
Selvin, Paul R.
树突状棘的超微结构：突触和脊柱形态之间的相关性。
影响因子：
4.3
作者：
Arellano JI;Benavides-Piccione R;Defelipe J;Yuste R
通讯作者：
Yuste R