Role of N-glycans in lateral diffusion of AMPA-type glutamate receptor in neuronal plasma membrane

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16074
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43030:Functional biochemistry-related
• Research Institution: Kyoto University
• Principal Investigator: Morise Jyoji 京都大学, 医学研究科, 助教 (60755669)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: AMPA型グルタミン酸受容体 / N型糖鎖 / 一分子イメージング法

Outline of Final Research Achievements

The number of AMPA-type glutamate receptors (AMPARs) regulates the excitatory transmission level between neurons. Therefore, the regulation of AMPARs number is important for understanding the molecular mechanisms of learning and memory formation. In particular, loss of a specific glycan structure on AMPARs reduced long-term potentiation, which is the basis of learning and memory formation. In this study, how specific N-glycans regulate the number of AMPARs was investigated by focusing on the AMPAR expression level and dynamics in neuronal plasma membrane. As a result, it was found that AMPARs, which have been believed to be stable as tetramers, repeatedly associated and dissociated between monomers and tetramers in the plasma membrane within several hundred milliseconds. Furthermore, specific N-glycans regulated the cell surface expression level of AMPARs.

Free Research Field

神経糖鎖生物学

Academic Significance and Societal Importance of the Research Achievements

これまでアルツハイマー病を代表とした脳機能疾患において、海馬領域での長期増強異常が見つかってきた。なかでも最近、ハンチントン病態モデルにおいて膜表面上でのAMPARの移動能に異常があることが報告された。そして興味深いことに、一部の統合失調患者で異常な糖鎖修飾がAMPARに観察されることも分かってきた。その中で本研究成果は特定の糖鎖構造がAMPARの動態にどのように影響を与えるかについて解析したものであり、糖鎖が疾患の原因分子である可能性や、新たな治療標的となりうる可能性を示した点で、重要な知見であると考える。