서보 암 - seobo am

서보암 (Bo Am Seo)
기초과학연구원, KAIST

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CV updated 2021-10-20 15:09

 

LARGE, an intellectual disability-associated protein, regulates AMPA-type glutamate receptor trafficking and memory

Authors and Affiliations

Abstract

Mutations in the human LARGE gene result in severe intellectual disability and muscular dystrophy. How LARGE mutation leads to intellectual disability, however, is unclear. In our proteomic study, LARGE was found to be a component of the AMPA-type glutamate receptor (AMPA-R) protein complex, a main player for learning and memory in the brain. Here, our functional study of LARGE showed that LARGE at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to down-regulated surface and synaptic AMPA-R targeting. In LARGE knockdown mice, long-term potentiation (LTP) was occluded by synaptic AMPA-R overloading, resulting in impaired contextual fear memory. These findings indicate that the fine-tuning of AMPA-R trafficking by LARGE at the Golgi is critical for hippocampus-dependent memory in the brain. Our study thus provides insights into the pathophysiology underlying cognitive deficits in brain disorders associated with intellectual disability.

intellectual disability | synaptic plasticity | AMPA receptor | LARGE

논문정보
- 형식: Research article
- 게재일: 2018년 06월 (BRIC 등록일 2018-06-20)
- 연구진: 국내(교신)+국외 연구진

- 분야: Neuroscience

 

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