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遠距離輸送のためのリソソームでRNA粒子をヒッチハイクし,アネキシンA11を分子テザーとして使用する

Ya-Cheng Liao¹, Michael S Fernandopulle², Guozhen Wang³

¹HHMI Janelia Research Campus, Ashburn, VA, USA.

|September 21, 2019

まとめ

科学者はアネキシンA11 (ANXA11) が RNAの粒子をニューロン内の長距離輸送のためにリスソームに結合することを発見しました ANXA11の変異は,このプロセスを妨害し,アミオトロフィック横筋硬化症 (ALS) と関連付けます.

科学分野:

細胞生物学
神経科学
分子生物学

背景:

ニューロンの局所的なタンパク質合成には,長距離RNA輸送が不可欠であり,適切な空間的なタンパク質組織を確保します.
ニューロンのような二極化された細胞は細胞機能の効率的なRNA輸送に依存しています

研究の目的:

リンソソームによって媒介されるRNA粒子の輸送のメカニズムを解明する.
移動するリソソームにRNA粒子を結合させる分子プレーヤーを特定する.
ニューロンのRNA伝達におけるアネキシンA11 (ANXA11) の役割と,アミオトロフィック横筋硬化症 (ALS) に対する影響を調査する.

主な方法:

分子相互作用を理解するための in vitro 生体物理モデリング
活細胞顕微鏡でRNA粒子の動態とライソソームの動態を可視化する.
相互作用するタンパク質を特定するために,偏りのない近接ラベリングプロテオミクス.

主要な成果:

アネキシンA11 (ANXA11) は,RNAの粒子をリソソームと結びつける分子結合体として作用する.
ANXA11の構造は,相分離を駆動するN末端領域と,膜結合するC末端領域で,その二重の役割を容易にする.
RNAの粒子の輸送はANXA11に依存し,ALSに関連した変異は,リゾソームの相互作用を妨害することによって,この輸送を損なう.

結論:

ANXA11は,RNAの粒子を活性輸送されたリソソームに結合させることで,ニューロンRNAの輸送を媒介する.
このANXA11に依存するメカニズムは細胞機能に不可欠であり,アミオトロフィック横筋硬化症 (ALS) で破壊される.
この発見はRNAの輸送調節と神経変性疾患のメカニズムに関する洞察を提供します.

キーワード:

ANXA11 についてアミオトロフィック・ラテラル・スクレロス地元の翻訳リソソーム神経変性ニューロンオーガネルの接触フェーズ分離 RNAの粒 RNA輸送

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