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.
Keywords: F-actin; STED; calcium; caldendrin; cofilin; cortactin; dendritic spines; synaptic plasticity.
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