Stim2-Eb3 Association and Morphology of Dendritic Spines in Hippocampal Neurons.
Stim2-Eb3 Association and Morphology of Dendritic Spines in Hippocampal Neurons.
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DOI：
10.1038/s41598-017-17762-8
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发表时间：
2017-12-15
影响因子：
4.6
通讯作者：
Bezprozvanny I
中科院分区：
文献类型：
--
作者：
Pchitskaya E;Kraskovskaya N;Chernyuk D;Popugaeva E;Zhang H;Vlasova O;Bezprozvanny I
蘑菇刺形成强大的突触接触，对于记忆存储至关重要。我们之前已经证明海马神经元中神经元库操纵的钙内流（nSOC）受 STIM2 蛋白调节。该通路在蘑菇刺的稳定性中发挥着关键作用，并且在不同的阿尔茨海默病（AD）小鼠模型中受到损害。肌动蛋白被认为是树突棘中存在的唯一细胞骨架区室，然而，最近的研究表明，带有 EB3 加帽正端的动态微管会短暂进入树突棘。我们发现 STIM2 通过 Ser-x-Ile-Pro 氨基酸基序与 EB3 形成内质网 (ER) Ca2+ 依赖性复合物，并且 STIM2-EB3 相互作用的破坏导致海马神经元蘑菇刺的损失。 EB3 的过度表达会导致蘑菇刺分数增加，并能够恢复从 PS1-M146V-KI AD 小鼠模型获得的海马神经元中蘑菇刺分数的缺陷。 EB3 敲低后，STIM2 过表达未能恢复蘑菇树突棘，而相反，EB3 过表达则挽救了因 STIM2 耗尽而导致的蘑菇树突棘损失。我们认为 EB3 参与树突棘形态的调节，部分原因是它与 STIM2 相关，并且调节 EB3 表达是克服 AD 期间突触损失的潜在方法。
Mushroom spines form strong synaptic contacts and are essential for memory storage. We have previously demonstrated that neuronal store-operated calcium entry (nSOC) in hippocampal neurons is regulated by STIM2 protein. This pathway plays a key role in stability of mushroom spines and is compromised in different mice models of Alzheimer’s disease (AD). Actin was thought to be the sole cytoskeleton compartment presented in dendritic spines, however, recent studies demonstrated that dynamic microtubules with EB3 capped plus-ends transiently enter spines. We showed that STIM2 forms an endoplasmic reticulum (ER) Ca2+ -dependent complex with EB3 via Ser-x-Ile-Pro aminoacid motif and that disruption of STIM2-EB3 interaction resulted in loss of mushroom spines in hippocampal neurons. Overexpression of EB3 causes increase of mushroom spines fraction and is able to restore their deficiency in hippocampal neurons obtained from PS1-M146V-KI AD mouse model. STIM2 overexpression failed to restore mushroom dendritic spines after EB3 knockdown, while in contrast EB3 overexpression rescued loss of mushroom spines resulting from STIM2 depletion. We propose that EB3 is involved in regulation of dendritic spines morphology, in part due to its association with STIM2, and that modulation of EB3 expression is a potential way to overcome synaptic loss during AD.
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影响因子：
19
作者：
Collins SR;Meyer T
通讯作者：
Meyer T
影响因子：
3.3
作者：
Garcia-Alvarez G;Lu B;Yap KA;Wong LC;Thevathasan JV;Lim L;Ji F;Tan KW;Mancuso JJ;Tang W;Poon SY;Augustine GJ;Fivaz M
通讯作者：
Fivaz M
影响因子：
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作者：
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通讯作者：
Hoogenraad, Casper C.
DOI：
10.1016/j.bbamcr.2015.01.019
发表时间：
2015-09-01
影响因子：
5.1
作者：
Majewski, Lukasz;Kuznicki, Jacek
通讯作者：
Kuznicki, Jacek
影响因子：
5.3
作者：
Hu, Xindao;Viesselmann, Chris;Dent, Erik W.
通讯作者：
Dent, Erik W.