Emmy Noether Group "Neuronal Protein Transport," Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany; RG Neuroplasticity, Leibniz-Institute for Neurobiology, Magdeburg 39118, Germany; Cell Biology, Faculty of Science, Utrecht University, Utrecht 3584 CH, the Netherlands.
Emmy Noether Group "Neuronal Protein Transport," Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg 20251, Germany; RG Neuroplasticity, Leibniz-Institute for Neurobiology, Magdeburg 39118, Germany.
Neuron. 2018 Mar 7;97(5):1110-1125.e14. doi: 10.1016/j.neuron.2018.01.046. Epub 2018 Feb 22.
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 Ca-transients are still poorly defined. We show that the postsynaptic Ca 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 [Ca] 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 [Ca] to preserve a minimal F-actin pool that is required for actin remodeling in the early phase of LTP.
钙依赖性可塑性的区室化允许树突棘中快速的肌动蛋白重塑。然而，通过棘突钙瞬变来时空调节丝状肌动蛋白（F-肌动蛋白）动力学的分子机制仍未得到很好的定义。我们表明，突触后钙传感器钙调蛋白协调纳米域肌动蛋白动力学，这对于长时程增强（LTP）早期的肌动蛋白重塑至关重要。棘突 [Ca] 的急剧升高破坏了钙调蛋白的分子内相互作用，并允许桩蛋白结合。这种相互作用的快速开启和缓慢关闭速率使桩蛋白保持在活性构象，并防止 F-肌动蛋白在棘突基部被肌球蛋白诱导的切断。钙调蛋白基因敲除导致突触肌动蛋白周转率增加，棘突 F-肌动蛋白的纳米尺度组织改变，结构棘突可塑性、LTP 和海马依赖学习的缺陷。总的来说，这些数据表明钙调蛋白-桩蛋白直接将 [Ca] 耦合起来，以维持最小的 F-肌动蛋白池，这是 LTP 早期肌动蛋白重塑所必需的。
