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Bi-directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity

Authors

  • Junko Iki,

    1. Department of Cell Biology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113–8519, Japan
    2. COE Program for Brain Integration and its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113–8519, Japan
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  • Akihiro Inoue,

    1. Department of Cell Biology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113–8519, Japan
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  • Haruhiko Bito,

    1. Department of Neurochemistry, the University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113–0033, Japan
    2. Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, 332–0012, Japan
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  • Shigeo Okabe

    1. Department of Cell Biology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113–8519, Japan
    2. Molecular Neurophysiology Group, Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, 305–8566, Japan
    3. Solution Oriented Research for Science and Technology (SORST), Japan Science and Technology Agency (JST), Kawaguchi, 332–0012, Japan
    4. COE Program for Brain Integration and its Disorders, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113–8519, Japan
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Dr Shigeo Okabe, 1Department of Cell Biology, as above.
E-mail: okabe.cbio@tmd.ac.jp

Abstract

Cortactin is an F-actin-associated protein which interacts with the postsynaptic scaffolding protein Shank at the SH3 domain and is localized within the dendritic spine in the mouse neuron. Green fluorescent protein (GFP)-based time-lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain-derived neurotrophic factor (BDNF). This response was mediated by mitogen-activated protein (MAP) kinase activation and was dependent on the C-terminal SH3 domain. In contrast, activation of N-methyl-d-aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. This NMDA-dependent redistribution was blocked by an Src family kinase inhibitor. Conversely, increasing Src family kinase activity induced cortactin phosphorylation and loss of cortactin from the postsynaptic sites. Finally, blocking of endogenous BDNF reduced the amount of cortactin at the postsynaptic sites and an NMDA receptor antagonist prevented this reduction. These results indicate the importance of counterbalance between BDNF and NMDA receptor-mediated signalling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.

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