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The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines

Author

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  • Zhuoyi Liang

    (The Hong Kong University of Science and Technology
    Molecular Neuroscience Center, The Hong Kong University of Science and Technology
    State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology)

  • Yi Zhan

    (The Hong Kong University of Science and Technology
    Molecular Neuroscience Center, The Hong Kong University of Science and Technology
    State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
    Present address: College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China)

  • Yang Shen

    (The Hong Kong University of Science and Technology
    Molecular Neuroscience Center, The Hong Kong University of Science and Technology
    State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology)

  • Catherine C. L. Wong

    (The Scripps Research Institute
    Present address: National Center for Protein Science (Shanghai), Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201210, China)

  • John R. Yates

    (State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
    The Scripps Research Institute)

  • Florian Plattner

    (University of Texas Southwestern Medical Center)

  • Kwok-On Lai

    (The Hong Kong University of Science and Technology
    Molecular Neuroscience Center, The Hong Kong University of Science and Technology
    State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology
    Present address: School of Biomedical Sciences and State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China)

  • Nancy Y. Ip

    (The Hong Kong University of Science and Technology
    Molecular Neuroscience Center, The Hong Kong University of Science and Technology
    State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology)

Abstract

Dendritic spine stabilization depends on afferent synaptic input and requires changes in actin cytoskeleton dynamics and protein synthesis. However, the underlying molecular mechanism remains unclear. Here we report the identification of ‘calmodulin kinase-like vesicle-associated’ (CaMKv), a pseudokinase of the CaMK family with unknown function, as a synaptic protein crucial for dendritic spine maintenance. CaMKv mRNA localizes at dendrites, and its protein synthesis is regulated by neuronal activity. CaMKv function is inhibited upon phosphorylation by cyclin-dependent kinase 5 (Cdk5) at Thr345. Furthermore, CaMKv knockdown in mouse hippocampal CA1 pyramidal neurons impairs synaptic transmission and plasticity in vivo, resulting in hyperactivity and spatial memory impairment. These findings collectively indicate that the precise regulation of CaMKv through activity-dependent synthesis and post-translational phosphorylation is critical for dendritic spine maintenance, revealing an unusual signalling pathway in the regulation of synaptic transmission and brain function that involves a pseudokinase.

Suggested Citation

  • Zhuoyi Liang & Yi Zhan & Yang Shen & Catherine C. L. Wong & John R. Yates & Florian Plattner & Kwok-On Lai & Nancy Y. Ip, 2016. "The pseudokinase CaMKv is required for the activity-dependent maintenance of dendritic spines," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13282
    DOI: 10.1038/ncomms13282
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