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Identification of Human Neuronal Protein Complexes Reveals Biochemical Activities and Convergent Mechanisms of Action in Autism Spectrum Disorders.


ABSTRACT: The prevalence of autism spectrum disorders (ASDs) is rapidly growing, yet its molecular basis is poorly understood. We used a systems approach in which ASD candidate genes were mapped onto the ubiquitous human protein complexes and the resulting complexes were characterized. The studies revealed the role of histone deacetylases (HDAC1/2) in regulating the expression of ASD orthologs in the embryonic mouse brain. Proteome-wide screens for the co-complexed subunits with HDAC1 and six other key ASD proteins in neuronal cells revealed a protein interaction network, which displayed preferential expression in fetal brain development, exhibited increased deleterious mutations in ASD cases, and were strongly regulated by FMRP and MECP2 causal for Fragile X and Rett syndromes, respectively. Overall, our study reveals molecular components in ASD, suggests a shared mechanism between the syndromic and idiopathic forms of ASDs, and provides a systems framework for analyzing complex human diseases.

SUBMITTER: Li J 

PROVIDER: S-EPMC4776331 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Identification of Human Neuronal Protein Complexes Reveals Biochemical Activities and Convergent Mechanisms of Action in Autism Spectrum Disorders.

Li Jingjing J   Ma Zhihai Z   Shi Minyi M   Malty Ramy H RH   Aoki Hiroyuki H   Minic Zoran Z   Phanse Sadhna S   Jin Ke K   Wall Dennis P DP   Zhang Zhaolei Z   Urban Alexander E AE   Hallmayer Joachim J   Babu Mohan M   Snyder Michael M  

Cell systems 20151101 5


The prevalence of autism spectrum disorders (ASDs) is rapidly growing, yet its molecular basis is poorly understood. We used a systems approach in which ASD candidate genes were mapped onto the ubiquitous human protein complexes and the resulting complexes were characterized. The studies revealed the role of histone deacetylases (HDAC1/2) in regulating the expression of ASD orthologs in the embryonic mouse brain. Proteome-wide screens for the co-complexed subunits with HDAC1 and six other key AS  ...[more]

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