title: The calcium sensor Copine-6 regulates spine structural plasticity and learning and memory.
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.
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Reinhard
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kriz
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Milos
authors.initials: M
authors.lastname: Galic
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Nico
authors.initials: N
authors.lastname: Angliker
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rajalu
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Kaspar E
authors.initials: KE
authors.lastname: Vogt
authors.affiliation: Biozentrum, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Ruegg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D020013:Calcium Signaling; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D017774:Long-Term Potentiation; D008565:Membrane Proteins / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D018345:Mice, Knockout; D016297:Mutagenesis, Site-Directed; D009473:Neuronal Plasticity; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C000607099:copine 6 protein, mouse; D020830:rac1 GTP-Binding Protein