クラスタ化されたプロトカデリン神経自己認識複合体の可視化
Julia Brasch1,2,3, Kerry M Goodman1,3, Alex J Noble2
1Zuckerman Mind, Brain and Behavior Institute, Columbia University, New York, NY, USA.
Nature
|April 12, 2019
まとめ
ニューライトの自己認識は,ジッパーのような構造を形成するクラスタ化されたプロトカデリンに依存しています. これらの分子組成は神経細胞の回避を媒介し 神経系の適切な発達と機能に不可欠です
科学分野:
- 神経科学
- 分子生物学
- 構造生物学
背景:
- 神経細胞の自己認識と回避は神経系の発達に不可欠であり, dendritic arborizationを誘導し,自己接続を防ぐ.
- クラスタ化されたプロトカデリン (PCDH) は,その多様な同型で個々のニューロンに独自のアイデンティティを提供し,自己認識を媒介する.
- 以前の研究では,プロトカデリンのシスとトランス相互作用を孤立的に特徴づけましたが,完全なエクトドメイン構造とニューロン表面の自己認識におけるその役割は不明でした.
研究 の 目的:
- 自己認識複合体の全長クラスターされたプロトカデリンエクトドメインの分子配置を決定する.
- プロトカデリンが神経の自己認識と回避を媒介する構造的基礎を解明する.
主な方法:
- クラスタ化されたプロトカデリン γB4 エクトドメインの構造を決定するために,X線結晶学を用いた.
- クリオ電子トモグラフィーは,リポソームのクラスター化されたプロトカデリン γB6 エクトドメインの組み立てを視覚化するために使用されました.
主要な成果:
- クラスター化されたプロトカデリン γB4の結晶構造は,交互にシスとトランス相互作用によって形成されたジッパーのような格子を示した.
- クリオ電子トモグラフィーは,クラスタ化されたプロトカデリン γB6 エクトドメインが膜接触部位で自発的に線形配列に組み合わさることを示した.
- これらの線形アセンブリは平行配列を形成し,結晶構造と一致する膜間のより大きな二次元構造を作成します.
結論:
- クラスタ化されたプロトカデリンによる秩序付けられた線形アセンブリの形成は,ニューロンの自己認識と回避における重要な初期段階である.
- これらの発見は,プロトカデリン媒介の自己認識のアイソフォーム不一致連鎖終結モデルを支持する.
- この研究は,プロトカデリンが神経細胞の境界を確立し,神経系の適切な配線を確保する方法に関する構造的な洞察を提供します.
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