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

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.

journal_name

Neuron

journal_title

Neuron

authors

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

doi

10.1016/j.neuron.2011.08.017

subject

Has Abstract

pub_date

2011-09-22 00:00:00

pages

1022-9

issue

6

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(11)00738-0

journal_volume

71

pub_type

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