LARGE, an AMPA receptor interactor, plays a large role in long-term memory formation by driving homeostatic scaling-down

Bo Am Seo, Taesup Cho, Daniel Z. Lee, Hwa Young Lee, Joong Jae Lee, Boyoung Lee, Seong Wook Kim, Kathryn A. Cunningham, Kelly T. Dineley, Thomas A. Green, Ho Min Kim, Se Young Choi, Hee Sup Shin, Myoung Goo Kang

Research output: Contribution to journalArticlepeer-review

Abstract

Dynamic trafficking of AMPA-type glutamate receptor (AMPA-R) in neuronal cells is a key cellular mechanism for learning and memory in the brain, which is regulated by AMPA-R interacting proteins. LARGE, a protein associated with intellectual disability, was found to be a novel component of the AMPA-R protein complex in our proteomic study. Here, our functional study of LARGE showed that during homeostatic scaling-down, increased LARGE expression at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to downregulated surface and synaptic AMPA-R targeting. In LARGE knockdown mice, long-term potentiation (LTP) was occluded by synaptic AMPA-R overloading, resulting in impaired long-term memory formation. These findings indicate that the fine-tuning of AMPA-R trafficking by LARGE at the Golgi is critical for memory stability in the brain. Our study thus provides novel insights into the pathophysiology of brain disorders associated with intellectual disability.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Dec 19 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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