Regulation of channel activity of AMPA receptors by membrane microdomains as revealed by high-resolution single-molecule imaging

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19521
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomedical structure and function and related fields
• Research Institution: Gifu University
• Principal Investigator: Suzuki Kenichi 岐阜大学, 研究推進・社会連携機構, 教授 (50423059)
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: AMPA受容体 / 1分子蛍光観察 / 超解像蛍光観察 / チャネル活性

Outline of Final Research Achievements

The purpose of this study is to unravel the distribution of AMPA receptors (AMPARs) and the mechanisms of synapse plasticity. Single-molecule observation in HEK203 cell plasma membranes revealed that AMPARs did not form stable tetramers, and even monomers existed. Furthermore, we found that AMPARs formed transient homodimers with a lifetime of about 100 ms in mouse neuronal membranes. The mobility of AMPARs was very slow in Homer 1b domain of synapse region, meanwhile some of AMPARs diffused rapidly outside of Homer 1b domains Based on these results, we propose a model that AMPARs alter the density in and out of the post-synapse upon stimulation and generate synapse plasticity, which is caused by the rapid mobility of AMPAR monomers.

Free Research Field

細胞生物物理学

Academic Significance and Societal Importance of the Research Achievements

本研究では、神経細胞間での情報伝達が起きているシナプスと言われる領域で、情報伝達の担い手である受容体が、刺激に応じて増減する機構を解明しようと試みた。神経細胞上で受容体の1分子ずつを観察した結果、受容体は今まで考えられてきたような安定な4量体ばかりではなく、短い寿命の2量体や単量体も多くみられた。シナプス領域中のHomer1bというタンパク質でできた膜領域では、受容体の運動は非常に遅かったが、その外では速い成分も存在していた。これらの結果から、刺激に応じて神経細胞がシナプス領域内外の受容体密度を迅速に変えることができるのは、受容体の単量体の速い動きが原因だというモデルを提案した。