title: 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.
authors.affiliation: Department of Neuroscience, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Lauren
authors.initials: L
authors.lastname: Makuch
authors.forename: Lenora
authors.initials: L
authors.lastname: Volk
authors.forename: Victor
authors.initials: V
authors.lastname: Anggono
authors.forename: Richard C
authors.initials: RC
authors.lastname: Johnson
authors.forename: Yilin
authors.initials: Y
authors.lastname: Yu
authors.forename: Kerstin
authors.initials: K
authors.lastname: Duning
authors.forename: Joachim
authors.initials: J
authors.lastname: Kremerskothen
authors.forename: Jun
authors.initials: J
authors.lastname: Xia
authors.forename: Kogo
authors.initials: K
authors.lastname: Takamiya
authors.forename: Richard L
authors.initials: RL
authors.lastname: Huganir
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003214:Conditioning, Classical / Q000502:physiology; D004594:Electrophysiology; D005239:Fear; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D007858:Learning / Q000502:physiology; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics* / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C498297:PICk1 protein, human; D010750:Phosphoproteins; D018091:Receptors, AMPA; C513637:WWC1 protein, human