Impaired actin dynamics and suppression of Shank2-mediated spine enlargement in cortactin knockout mice

Author:

Tanaka Shinji1,Masuda Yasutaka1,Harada Akihiro2,Okabe Shigeo1

Affiliation:

1. Department of Cellular Neurobiology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo Bunkyo-ku, Tokyo 113-0033, Japan

2. Department of Cell Biology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan

Abstract

Abstract Cortactin regulates actin polymerization and stabilizes branched actin network. In neurons, cortactin is enriched in dendritic spines that contain abundant actin polymers. To explore the function of cortactin in dendritic spines, we examined spine morphology and dynamics in cultured neurons taken from cortactin knockout (KO) mice. Histological analysis revealed that the density and morphology of dendritic spines were not significantly different between wild-type (WT) and cortactin KO neurons. Time-lapse imaging of hippocampal slice cultures showed that the extent of spine volume change was similar between WT and cortactin KO neurons. Despite little effect of cortactin deletion on spine morphology and dynamics, actin turnover in dendritic spines was accelerated in cortactin KO neurons. Furthermore, we detected a suppressive effect of cortactin KO on spine head size under the condition of excessive spine enlargement induced by overexpression of a prominent postsynaptic density protein Shank2. These results suggest that cortactin may have a role in maintaining actin organization by stabilizing actin filaments near the postsynaptic density.

Funder

Scientific Research

Core Research for Evolutional Science and Technology

Japanese Science and Technology Agency

Project for Elucidating and Controlling Mechanisms of Aging and Longevity

Japan Agency for Medical Research and Development

Utokyo

Publisher

Oxford University Press (OUP)

Subject

Radiology Nuclear Medicine and imaging,Instrumentation,Structural Biology

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