Hippocalcin functions as a calcium sensor in hippocampal LTD.
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.
Palmer
Claire L
CL
MRC Centre for Synaptic Plasticity, Department of Anatomy, School of Medical Sciences, University of Bristol, Bristol, BS8 1TD, United Kingdom.
Lim
Wonil
W
Hastie
Peter G R
PG
Toward
Marie
M
Korolchuk
Viktor I
VI
Burbidge
Stephen A
SA
Banting
George
G
Collingridge
Graham L
GL
Isaac
John T R
JT
Henley
Jeremy M
JM
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
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