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

Neuron
Marina MikhaylovaMichael R Kreutz

Abstract

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+]idisrupts 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+]ito preserve a minimal F-actin pool that is required for actin remodeling in the early phase of LTP.

Citations

Mar 6, 2019·Cold Spring Harbor Perspectives in Biology·Robert D BurgoyneLee P Haynes
Aug 3, 2019·Journal of Cell Science·Anja KonietznyMarina Mikhaylova
Oct 5, 2019·ELife·Andrea Cuentas-CondoriDavid M Miller
Nov 26, 2019·Cytoskeleton·Michael BucherMarina Mikhaylova
Aug 4, 2018·Frontiers in Cell and Developmental Biology·Edgar AngelatsGemma Navarro
Dec 1, 2019·Nature Communications·Maria Andres-AlonsoMichael R Kreutz
Feb 23, 2019·Frontiers in Molecular Neuroscience·Jennifer MundhenkMichael R Kreutz
Feb 2, 2020·Nature Communications·Kubra Gulmez KaracaAna M M Oliveira
Sep 3, 2019·Frontiers in Cellular Neuroscience·Mona Katrin RoeslerWolfgang Wagner
Mar 16, 2021·The Journal of General Physiology·Kazuki ObashiShigeo Okabe
Sep 18, 2020·Current Opinion in Neurobiology·Swathi Shivaram SuratkalJun Nishiyama

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