Caldendrin Directly Couples Postsynaptic Calcium Signals to Actin Remodeling in Dendritic Spines

• DOI: 10.1016/j.neuron.2018.01.046
• Publication Date: 2018-02-23T17:19:57Z
• Authors: Marina Mikhaylova; Julia Bär; Bas van Bommel; Philipp Schätzle; PingAn YuanXiang; Rajeev Raman; Johannes Hradsky; Anja Konietzny; Egor Y. Loktionov; Pasham Parameshwa...; Jeffrey Lopez-Rojas; Christina Spilker; Oliver Kobler; Syed Ahsan Raza; Oliver Stork; Casper C. Hoogenraad; Michael R. Kreutz
• Keywords: Actin remodeling; Cortactin; Cofilin

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.