後期エンドソームはmRNA翻訳プラットフォームとして作用し,軸索内のミトコンドリアを維持する

Jean-Michel Cioni¹, Julie Qiaojin Lin¹, Anne V Holtermann¹

¹Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3DY, UK.

Cell

|January 8, 2019

まとめ

ニューロンの健康には極めて重要です研究者らは後期エンドソームがタンパク質合成のハブとして働き,RNA,リボソーム,ミトコンドリアを結合させ軸索の活性を維持することを発見しました

科学分野:

神経科学
細胞生物学
分子生物学

背景:

ニューロンの配線と維持には,mRNAの局所的な翻訳が不可欠です.
軸索のmRNAの局所化と翻訳のメカニズムはほとんど不明である.

研究の目的:

エンドソームがアクソナルmRNAの局所化と局所タンパク質の合成における役割を調査する.
アクソナル翻訳に関与する特定のエンドソーマル経路を特定する.

主な方法:

網膜のギャングリオン細胞のアクソンをリアルタイムで撮影しました
RNAの粒,リボソーム,ミトコンドリアとエンドソームの関連性を調査した.
アクソンタンパク質の合成と機能への影響を評価するためにRab7a変異体を使用した.

主要な成果:

アクソン内のラブ7a末端エンドソームに関連したRNA粒子を特定した.
Rab7aの遅いエンドソームは,ミトコンドリアのタンパク質を翻訳する局所的なタンパク質合成の場所であることを示した.
Rab7aの機能の障害は,特にシャーコット・マリー・トゥース型2B神経症に関連した変異体で,軸索タンパク質合成,ミトコンドリア機能,および生存能力を損なうことが示された.

結論:

後期エンドソームは,軸索における局所的なタンパク質合成の重要なプラットフォームとして機能する.
このプロセスは,エンドソーム,RNAの粒,リボソーム,ミトコンドリアの連携した相互作用を伴う.
このエンドソーム媒介の翻訳の調節不良は,軸索の健康に影響を与え,シャルコ・マリー・トゥース2B型神経症のような神経変性疾患に関与しています.

キーワード:

シャーコ・マリー・トゥース型2B RNAの密輸アクソン維持エンドソーム局所タンパク質合成リソソーム mRNA翻訳ミトコンドリア網膜のギャングリオン細胞

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