2011 Fiscal Year Final Research Report
CADM1, a molecule linked to Autism Spectrum Disorder, forms a synaptic complex and its function.
| Project/Area Number |
21500334
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | International University of Health and Welfare |
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Principal Investigator |
MOMOI Takashi 国際医療福祉大学, 保健医療学部, 教授 (40143507)
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| Project Period (FY) |
2009 – 2011
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| Keywords | シナプス / Cadm1 / 自閉症 |
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| Research Abstract |
Autism spectrum disorder (ASD), a neurodevelopmental disorder of uncertain molecular origin, has been previously linked to mutations in synaptic adhesion molecules, animbalance of excitatory and inhibitory synapses, and/or an impaired cerebellum. Mutations in the synaptic adhesion protein CADM1 (RA175/SynCAM1) are associated with ASD, and Cadm1 knock out (KO) mice exhibit smaller cerebella with decreased number of synapse of Purkinje cells and some ASD-like symptoms, including impaired ultrasonic vocalization. In the present study, we examined the alteration of the Cadm1 synaptic complex in the mouse cerebellum at postnatal stages. The C-terminal peptide of Cadm1 associated with Mupp1 at PDZ(1-5), a scaffold protein containing 13 PDZ domains, which interacted with GABBR2 at PDZ13, but not with PSD-95. Cadm1 co-localized with Mupp1 and GABBR2 on the dendrites of hippocampal neurons cultured in vitro and in the molecular layers of the cerebellum. These observations suggest that the Cadm1 synaptic receptor complex,including Mupp1-GABBR2, is located on the dendrites of Purkinje cells. The amount of GABBR2 protein but not mRNA was increased in the cerebella of Cadm1 KO mice, suggesting that lack of Cadm1 does not affect transcription but may stabilize the Mupp1-GABBR2 receptor complex. Up-regulation of GABBR2 in the cerebellum in the absence of CADM1 may be associated with ASD pathogenesis.
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Research Products
(11 results)
