CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation.

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ID: 86636
2019
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Abstract
Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with symptoms including social deficits, anxiety, and communication difficulties. However, ASD pathogenic mechanisms are poorly understood. Mutations of CUL3, which encodes Cullin 3 (CUL3), a component of an E3 ligase complex, are thought of as risk factors for ASD and schizophrenia (SCZ). CUL3 is abundant in the brain, yet little is known of its function. Here, we show that CUL3 is critical for neurodevelopment. CUL3-deficient mice exhibited social deficits and anxiety-like behaviors with enhanced glutamatergic transmission and neuronal excitability. Proteomic analysis revealed eIF4G1, a protein for Cap-dependent translation, as a potential target of CUL3. ASD-associated cellular and behavioral deficits could be rescued by pharmacological inhibition of the eIF4G1 function and chemogenetic inhibition of neuronal activity. Thus, CUL3 is critical to neural development, neurotransmission, and excitation-inhibition (E-I) balance. Our study provides novel insight into the pathophysiological mechanisms of ASD and SCZ.
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dong2019cul3neuron Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Dong, Zhaoqi;Chen, Wenbing;Chen, Chao;Wang, Hongsheng;Cui, Wanpeng;Tan, Zhibing;Robinson, Heath;Gao, Nannan;Luo, Bin;Zhang, Lei;Zhao, Kai;Xiong, Wen-Cheng;Mei, Lin;
Journal neuron
Year 2019
DOI
S0896-6273(19)30930-4
URL
Keywords
schizophrenia offspring resting-state functional connectivity familial high-risk mvpa stg

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