CAMDI interacts with the human memory-associated protein KIBRA and regulates AMPAR cell surface expression and cognition

Little is known about the molecular mechanisms of cognitive deficits in psychiatric disorders. CAMDI is a psychiatric disorder-related factor, the deficiency of which in mice results in delayed neuronal migration and psychiatrically abnormal behaviors. Here, we found that CAMDI-deficient mice exhibi...

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Bibliographic Details
Published in:PloS one 2019-11, Vol.14 (11), p.e0224967-e0224967
Main Authors: Fukuda, Toshifumi, Nagashima, Shun, Inatome, Ryoko, Yanagi, Shigeru
Format: Article
Language:English
Subjects:
Animal cognition
Animals
Behavior
Biochemistry
Biology and Life Sciences
Cell activation
Cell Line, Tumor
Cell Membrane - metabolism
Cell migration
Cell surface
Cognition
Cognitive ability
Cytosol
EDTA
Endocytosis
Genomes
Hippocampus
Humans
Internalization
Intracellular Signaling Peptides and Proteins - metabolism
Kinases
Laboratories
Leukocyte migration
Life sciences
Long-Term Potentiation
Medicine and Health Sciences
Memory
Mental disorders
Mice, Knockout
Molecular modelling
Nerve Tissue Proteins - metabolism
Neurons
Novels
Organic chemistry
Peptides
Pharmacy
Phosphoproteins - metabolism
Polyclonal antibodies
Propionic acid
Protein Binding
Proteins
Psychosis
rab GTP-Binding Proteins - metabolism
Receptors, AMPA - metabolism
Research and Analysis Methods
Schizophrenia
Spatial Memory
α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
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Summary:Little is known about the molecular mechanisms of cognitive deficits in psychiatric disorders. CAMDI is a psychiatric disorder-related factor, the deficiency of which in mice results in delayed neuronal migration and psychiatrically abnormal behaviors. Here, we found that CAMDI-deficient mice exhibited impaired recognition memory and spatial reference memory. Knockdown of CAMDI in hippocampal neurons increased the amount of internalized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) and attenuated the chemical long-term potentiation (LTP)-dependent cell surface expression of AMPAR. KIBRA was identified as a novel CAMDI-binding protein that retains AMPAR in the cytosol after internalization. KIBRA inhibited CAMDI-dependent Rab11 activation, thereby attenuating AMPAR cell surface expression. These results suggest that CAMDI regulates AMPAR cell surface expression during LTP. CAMDI dysfunction may partly explain the mechanism underlying cognitive deficits in psychiatric diseases.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0224967