CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation (Neuron 2020, 105:1-16)

報告日期: 2020/04/24
報告時間: 15:10/16:00
報告學生: 孫莉涵(英文報告)
講評老師: 陳柏熹
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CUL3 Deficiency Causes Social Deficits and Anxiety-like Behaviors by Impairing Excitation-Inhibition Balance through the Promotion of Cap-Dependent Translation

Neuron, February 5, 2020

Speaker: Li-Han Sun / 孫莉涵

Commentator: Po-See Chen Ph.D. /陳柏熹 博士

Time and Date: 15:10-16:00, April 24, 2020

Neurodevelopmental disorders are a group of disorders due to an abnormal brain development or damage, leading to abnormal brain function which may affect emotion, learning ability, or self-control. However, the pathological mechanisms of these neurodevelopmental disorders are still unclear. Here, the authors focus on Cullin 3 (CUL3), a component of the CUL3-RING E3 ubiquitin ligase complex, which regulates several cell functions such as anti-oxidation, cell cycle, protein trafficking, and signal transduction. Interestingly, many studies indicate that CUL3 is critical for autism spectrum disorders (ASD) and schizophrenia (SCZ) although the role in the nervous system is still unclear. First, the authors used the CUL3-deficient mice modle to show the results of social deficits and axiety-like behaviors by enhanced glutamatergic transmission and neuronal excitability. Second, they used the proteomic analysis to find which factors are associated with CUL3 in this case. The results indicated elF4G1, a target protein of CUL3 for Cap-dependent translation, as a critical one. Last, they used pharmacological inhibition of the elF4G1 function and chemogenetic inhibition of neuronal activity to demonstrate the importance. In conclusion, the authors provide novel insight into the pathophysiological mechanisms of ASD and SCZ and the critical role of CUL3 in neural development, neurotransmission, and excitation-inhibition (E-I) balance.

Key words:

Cullin 3, social deficit, anxiety, elF4G1