BROWSE

Related Scientist

Researcher

인지 및 사회성 연구단
인지 및 사회성 연구단
more info

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

Cited 0 time in webofscience Cited 0 time in scopus
137 Viewed 18 Downloaded
Title
LARGE, an intellectual disability-associated protein, regulates AMPA-type glutamate receptor trafficking and memory
Author(s)
Bo Am Seo; Taesup Cho; Daniel Z. Lee; Joong-jae Lee; Boyoung Lee; Seong-Wook Kim; Hee-Sup Shin; Myoung-Goo Kang
Publication Date
2018-07
Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-PHYSICAL SCIENCES, v.115, no.27, pp.7111 - 7116
Publisher
NATL ACAD SCIENCES
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. © 2018 National Academy of Sciences. All Rights Reserved
URI
https://pr.ibs.re.kr/handle/8788114/4874
ISSN
0027-8424
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
Files in This Item:
185. LARGE, an intellectual disability-associated protein, regulates AMPA-type glutamate receptor trafficking and memory.pdfDownload

qrcode

  • facebook

    twitter

  • Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse