Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Line, Tumor
-
Cell Membrane / metabolism*
-
Cognition*
-
Endocytosis
-
Humans
-
Intracellular Signaling Peptides and Proteins / metabolism*
-
Long-Term Potentiation
-
Memory*
-
Mice, Knockout
-
Nerve Tissue Proteins / metabolism*
-
Phosphoproteins / metabolism*
-
Protein Binding
-
Receptors, AMPA / metabolism*
-
Spatial Memory
-
rab GTP-Binding Proteins / metabolism
Substances
-
CCDC141 protein, mouse
-
Intracellular Signaling Peptides and Proteins
-
Nerve Tissue Proteins
-
Phosphoproteins
-
Receptors, AMPA
-
Wwc1 protein, mouse
-
rab11 protein
-
rab GTP-Binding Proteins
Grants and funding
This study was supported in part by Grants-in-Aid for scientific research from the Ministry of Education, Culture, Sports, Science, and Technology (18H04869) and the Japan Society for the Promotion of Science (17K08793 to T.F. and 17H04053 to S.Y.). T.F. was supported by grant from the Takeda Science Foundation. S.Y. was supported by AMED under Grant Number JP17gm5010002. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.