Impaired actin dynamics and suppression of Shank2-mediated spine enlargement in cortactin knockout mice
Impaired actin dynamics and suppression of Shank2-mediated spine enlargement in cortactin knockout mice
复制标题
Cortactin 敲除小鼠中肌动蛋白动力学受损和 Shank2 介导的脊柱增大受到抑制
DOI：
10.1093/jmicro/dfaa001
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发表时间：
2020
期刊：
影响因子：
1.8
通讯作者：
Okabe Shigeo
中科院分区：
文献类型：
--
作者：
Tanaka Shinji;Masuda Yasutaka;Harada Akihiro;Okabe Shigeo
Corpine调节肌动蛋白聚合并稳定分支肌动蛋白网络。在神经元中，皮质素在含有丰富肌动蛋白聚合物的树突棘中富集。为了探讨coronin在树突棘中的功能，我们研究了coronin敲除（KO）小鼠培养神经元的棘形态学和动力学。组织学分析显示，树突棘的密度和形态在野生型（WT）和coronin KO神经元之间没有显著差异。海马切片培养物的延时成像显示WT和coronin KO神经元之间的棘体积变化程度相似。尽管coronin缺失对棘形态学和动力学的影响不大，但coronin KO神经元中树突棘中的肌动蛋白周转加快。此外，我们检测到一个抑制作用的corneumn KO脊髓头部的大小过度脊髓扩大的条件下诱导的一个突出的突触后密度蛋白Shank2的过表达。这些结果表明，coronin可能有一个稳定的肌动蛋白丝附近的突触后密度在维持肌动蛋白组织的作用。
Cortactin regulates actin polymerization and stabilizes branched actin network. In neurons, cortactin is enriched in dendritic spines that contain abundant actin polymers. To explore the function of cortactin in dendritic spines, we examined spine morphology and dynamics in cultured neurons taken from cortactin knockout (KO) mice. Histological analysis revealed that the density and morphology of dendritic spines were not significantly different between wild-type (WT) and cortactin KO neurons. Time-lapse imaging of hippocampal slice cultures showed that the extent of spine volume change was similar between WT and cortactin KO neurons. Despite little effect of cortactin deletion on spine morphology and dynamics, actin turnover in dendritic spines was accelerated in cortactin KO neurons. Furthermore, we detected a suppressive effect of cortactin KO on spine head size under the condition of excessive spine enlargement induced by overexpression of a prominent postsynaptic density protein Shank2. These results suggest that cortactin may have a role in maintaining actin organization by stabilizing actin filaments near the postsynaptic density.