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 caldendrin-cortactin directly couple [Ca²⁺]_i to preserve a minimal F-actin pool that is required for actin remodeling in the early phase of LTP.

中文翻译：

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Caldendrin直接耦合突触后钙信号与树突棘肌动蛋白重塑。

钙依赖性可塑性的区室化使树突棘中的肌动蛋白快速重塑。然而，通过Ca ²⁺瞬态调节时空调节丝状肌动蛋白（F-肌动蛋白）动力学的分子机制仍然不明确。我们显示突触后钙²⁺传感器Caldendrin编排的纳米域肌动蛋白动力学，对于长期增强（LTP）早期的肌动蛋白重塑至关重要。棘突[Ca ²⁺ ] _i中的陡峭升高干扰降钙素的分子内相互作用，并允许皮质激素结合。这种相互作用的快开和慢停速率使cortactin保持活性构象，并保护脊柱底部的F-actin免受cofilin诱导的切断作用。Caldendrin基因敲除导致更高的突触肌动蛋白更新，改变的棘突肌动蛋白的纳米级组织，结构脊柱可塑性，LTP和海马依赖性学习中的缺陷。总体而言，数据表明，钙调蛋白-coractactin直接与[Ca ²⁺ ] _i耦合，以保留LTP早期肌动蛋白重塑所需的最小F-actin库。