title: Hippocalcin functions as a calcium sensor in hippocampal LTD.
abstract: It is not fully understood how NMDAR-dependent LTD causes Ca(2+)-dependent endocytosis of AMPARs. Here we show that the neuronal Ca(2+) sensor hippocalcin binds the beta2-adaptin subunit of the AP2 adaptor complex and that along with GluR2 these coimmunoprecipitate in a Ca(2+)-sensitive manner. Infusion of a truncated mutant of hippocalcin (HIP(2-72)) that lacks the Ca(2+) binding domains prevents synaptically evoked LTD but has no effect on LTP. These data indicate that the AP2-hippocalcin complex acts as a Ca(2+) sensor that couples NMDAR-dependent activation to regulated endocytosis of AMPARs during LTD.
authors.affiliation: MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Palmer
authors.forename: Wonil
authors.initials: W
authors.lastname: Lim
authors.forename: Peter G R
authors.initials: PG
authors.lastname: Hastie
authors.forename: Marie
authors.initials: M
authors.lastname: Toward
authors.forename: Viktor I
authors.initials: VI
authors.lastname: Korolchuk
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Burbidge
authors.forename: George
authors.initials: G
authors.lastname: Banting
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
authors.forename: John T R
authors.initials: JT
authors.lastname: Isaac
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Henley
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D033966:Adaptor Protein Complex beta Subunits / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D051597:Hippocalcin; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009924:Organ Culture Techniques; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D033962:Adaptor Protein Complex 2; D033966:Adaptor Protein Complex beta Subunits; D002135:Calcium-Binding Proteins; C496691:HPCA protein, human; C496693:Hpca protein, rat; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D051597:Hippocalcin; C104722:glutamate receptor ionotropic, AMPA 2; D002118:Calcium