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Publication : Regulation of AMPA receptor function by the human memory-associated gene KIBRA.

First Author  Makuch L Year  2011
Journal  Neuron Volume  71
Issue  6 Pages  1022-9
PubMed ID  21943600 Mgi Jnum  J:178552
Mgi Id  MGI:5299270 Doi  10.1016/j.neuron.2011.08.017
Citation  Makuch L, et al. (2011) Regulation of AMPA receptor function by the human memory-associated gene KIBRA. Neuron 71(6):1022-9
abstractText  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 alpha-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.
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