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

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.

Pubmed ID: 21943600

Authors

  • Makuch L
  • Volk L
  • Anggono V
  • Johnson RC
  • Yu Y
  • Duning K
  • Kremerskothen J
  • Xia J
  • Takamiya K
  • Huganir RL

Journal

Neuron

Publication Data

September 22, 2011

Associated Grants

  • Agency: NIMH NIH HHS, Id: MH64856
  • Agency: NINDS NIH HHS, Id: NS36715
  • Agency: NIMH NIH HHS, Id: R01 MH064856
  • Agency: NIMH NIH HHS, Id: R01 MH064856-10
  • Agency: NINDS NIH HHS, Id: R01 NS036715
  • Agency: NINDS NIH HHS, Id: R01 NS036715-14
  • Agency: NEI NIH HHS, Id: T32 EY017203
  • Agency: NIMH NIH HHS, Id: T32MH15330
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Behavior, Animal
  • Carrier Proteins
  • Cells, Cultured
  • Conditioning, Classical
  • Electrophysiology
  • Fear
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Learning
  • Male
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuronal Plasticity
  • Neurons
  • Nuclear Proteins
  • Phosphoproteins
  • Receptors, AMPA