Regulation of AMPA Receptor Function by the Human Memory-Associated Gene KIBRA

Lauren Makuch, Lenora Volk, Victor Anggono, Richard C. Johnson, Yilin Yu, Kerstin Duning, Joachim Kremerskothen, Jun Xia, Kogo Takamiya, Richard L. Huganir

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80 Scopus citations

Abstract

KIBRA has recently been identified as a gene associated with human memory performance. Despite the elucidation of the role of KIBRA in several diverse processes in nonneuronal cells, the molecular function of KIBRA in neurons is unknown. We found that KIBRA directly binds to the protein interacting with C-kinase 1 (PICK1) and forms a complex with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptors (AMPARs), the major excitatory neurotransmitter receptors in the brain. KIBRA knockdown accelerates the rate of AMPAR recycling following N-methyl-D-aspartate receptor-induced internalization. Genetic deletion of KIBRA in mice impairs both long-term depression and long-term potentiation at hippocampal Schaffer collateral-CA1 synapses. Moreover, KIBRA knockout mice have severe deficits in contextual fear learning and memory. These results indicate that KIBRA regulates higher brain function by regulating AMPAR trafficking and synaptic plasticity.

Original languageEnglish (US)
Pages (from-to)1022-1029
Number of pages8
JournalNeuron
Volume71
Issue number6
DOIs
StatePublished - Sep 22 2011

ASJC Scopus subject areas

  • Neuroscience(all)

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    Makuch, L., Volk, L., Anggono, V., Johnson, R. C., Yu, Y., Duning, K., Kremerskothen, J., Xia, J., Takamiya, K., & Huganir, R. L. (2011). Regulation of AMPA Receptor Function by the Human Memory-Associated Gene KIBRA. Neuron, 71(6), 1022-1029. https://doi.org/10.1016/j.neuron.2011.08.017