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The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory

Author

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  • Judith R. Reinhard

    (Biozentrum, University of Basel)

  • Alexander Kriz

    (Biozentrum, University of Basel)

  • Milos Galic

    (Biozentrum, University of Basel
    Present address: Institute of Medical Physics and Biophysics, DFG Cluster of Excellence ‘Cells in Motion’ (EXC 1003), University of Münster, 48149 Münster, Germany)

  • Nico Angliker

    (Biozentrum, University of Basel)

  • Mathieu Rajalu

    (Biozentrum, University of Basel)

  • Kaspar E. Vogt

    (Biozentrum, University of Basel
    Present address: International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Ibaraki 305 8575, Japan.)

  • Markus A. Ruegg

    (Biozentrum, University of Basel)

Abstract

Hippocampal long-term potentiation (LTP) represents the cellular response of excitatory synapses to specific patterns of high neuronal activity and is required for learning and memory. Here we identify a mechanism that requires the calcium-binding protein Copine-6 to translate the initial calcium signals into changes in spine structure. We show that Copine-6 is recruited from the cytosol of dendrites to postsynaptic spine membranes by calcium transients that precede LTP. Cpne6 knockout mice are deficient in hippocampal LTP, learning and memory. Hippocampal neurons from Cpne6 knockouts lack spine structural plasticity as do wild-type neurons that express a Copine-6 calcium mutant. The function of Copine-6 is based on its binding, activating and recruiting the Rho GTPase Rac1 to cell membranes. Consistent with this function, the LTP deficit of Cpne6 knockout mice is rescued by the actin stabilizer jasplakinolide. These data show that Copine-6 links activity-triggered calcium signals to spine structural plasticity necessary for learning and memory.

Suggested Citation

  • Judith R. Reinhard & Alexander Kriz & Milos Galic & Nico Angliker & Mathieu Rajalu & Kaspar E. Vogt & Markus A. Ruegg, 2016. "The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11613
    DOI: 10.1038/ncomms11613
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