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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Protein Complex 2 / metabolism*
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Adaptor Protein Complex beta Subunits / metabolism
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Animals
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Calcium / metabolism
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Calcium Signaling / physiology*
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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HeLa Cells
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Hippocalcin
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Hippocampus / metabolism*
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Humans
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Long-Term Synaptic Depression / physiology*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Organ Culture Techniques
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Protein Structure, Tertiary / physiology
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Rats
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Receptors, AMPA / metabolism*
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Receptors, N-Methyl-D-Aspartate / metabolism
Substances
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Adaptor Protein Complex 2
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Adaptor Protein Complex beta Subunits
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Calcium-Binding Proteins
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HPCA protein, human
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Hpca protein, rat
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Nerve Tissue Proteins
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Receptors, AMPA
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Receptors, N-Methyl-D-Aspartate
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Hippocalcin
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glutamate receptor ionotropic, AMPA 2
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Calcium