Caldendrin Directly Couples Postsynaptic Calcium Signals to Actin Remodeling in Dendritic Spines
Caldendrin Directly Couples Postsynaptic Calcium Signals to Actin Remodeling in Dendritic Spines
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DOI：
10.1016/j.neuron.2018.01.046
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发表时间：
2018-03-07
期刊：
影响因子：
16.2
通讯作者：
Kreutz, Michael R.
中科院分区：
文献类型：
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作者：
Mikhaylova, Marina;Baer, Julia;Kreutz, Michael R.
钙依赖性可塑性的区隔化允许树突棘中肌动蛋白的快速重塑。然而，棘状Ca2+瞬态对丝状肌动蛋白（F-actin）动力学的时空调节的分子机制仍然不明确。我们发现突触后Ca2+传感器caldendrin协调纳米结构域肌动蛋白动力学，这对于长期增强（LTP）早期肌动蛋白重塑至关重要。棘突[Ca2+](i)的急剧升高破坏了橄榄树蛋白的分子内相互作用，并允许接触结合。这种相互作用的快速开启和缓慢关闭速率使接触保持活跃构象，并保护脊柱基部的f -肌动蛋白免受cofilin诱导的切断。Caldendrin基因敲除导致突触肌动蛋白更新增加，棘f -肌动蛋白纳米级组织改变，脊柱结构可塑性缺陷，LTP和海马依赖学习。总的来说，这些数据表明，calden-drin- contact直接偶联[Ca2+](i)，以保持最小的f -肌动蛋白库，这是LTP早期肌动蛋白重塑所需的。
Compartmentalization of calcium-dependent plasticity allows for rapid actin remodeling in dendritic spines. However, molecular mechanisms for the spatio-temporal regulation of filamentous actin (F-actin) dynamics by spinous Ca2+-transients are still poorly defined. We show that the postsynaptic Ca2+ sensor caldendrin orchestrates nano-domain actin dynamics that are essential for actin remodeling in the early phase of long-term potentiation (LTP). Steep elevation in spinous [Ca2+](i) disrupts an intramolecular interaction of caldendrin and allows cortactin binding. The fast on and slow off rate of this interaction keeps cortactin in an active conformation, and protects F-actin at the spine base against cofilin-induced severing. Caldendrin gene knockout results in higher synaptic actin turnover, altered nanoscale organization of spinous F-actin, defects in structural spine plasticity, LTP, and hippocampus-dependent learning. Collectively, the data indicate that calden-drin-cortactin directly couple [Ca2+](i) to preserve a minimal F-actin pool that is required for actin remodeling in the early phase of LTP.