Open AccessThe calcium sensor Copine-6 regulates spine structural plasticity and learning and memory
Author(s) -
Judith Reinhard,
Alexander Kriz,
Milos Galic,
Nico Angliker,
Mathieu Rajalu,
Kaspar E. Vogt,
Markus A. Rüegg
Publication year - 2016
Publication title -
nature communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.559
H-Index - 365
ISSN - 2041-1723
DOI - 10.1038/ncomms11613
Subject(s) - long term potentiation , neuroscience , calcium signaling , microbiology and biotechnology , dendritic spine , hippocampal formation , synaptic plasticity , knockout mouse , calcium , cytosol , postsynaptic potential , biology , calcium imaging , chemistry , signal transduction , biochemistry , receptor , enzyme , organic chemistry
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.