進化的に保存されたリボソーム救済経路は,表皮の恒常性を維持する

Kifayathullah Liakath-Ali^1,2, Eric W Mills³, Inês Sequeira¹

¹Centre for Stem Cells and Regenerative Medicine, King's College London, London, UK.

Nature

|April 13, 2018

まとめ

ペロタ (Pelo) タンパク質は哺乳類の皮膚幹細胞の健康に不可欠です. 細胞の制御不能な成長と分化が原因で組織ホメオスタシスの役割を強調しています

科学分野:

分子生物学
細胞生物学
発達生物学

背景:

リボソーム関連 mRNA の品質管理は,タンパク質の翻訳精度にとって不可欠です.
酵母で研究されているが,哺乳類の組織,特に幹細胞の運命におけるその役割はあまり理解されていない.
ペロタ (Pelo) は進化的に保存されたタンパク質で停止したリボソームを救出します

研究の目的:

哺乳類の表皮性ホメオスタシスにおけるペロタ (Pelo) の役割を調査する.
ネズミの表皮の異なる幹細胞集団にPeloの消去の影響を決定する.
組織維持におけるペロの機能の基礎にある分子メカニズムを解明する.

主な方法:

ネズミの特定の表皮幹細胞集団 (Lrig1+,Lgr5+,Lgr6+) でPeloの条件付消去除
細胞増殖,分化,リボソーム足跡の蓄積の分析
グローバル翻訳率と遺伝子発現の評価
ラパミシンによるmTOR経路の薬理学的抑制

主要な成果:

Lrig1 を発現する皮質幹細胞におけるPeloの条件付消去は,過剰増殖と異常な分化をもたらした.
ペロの消去は短いリボソームの足跡の蓄積とグローバル翻訳のアップレギュレーションを引き起こした.
mTORのダウンレギュレーションによるトランスレーション阻害は表皮のフェノタイプを救った.
Lgr5 を発現する幹細胞への影響は最小で,Lgr6 を発現する幹細胞への影響は軽かった.

結論:

ペロタ (Pelo) は哺乳類の表皮平衡を維持するために不可欠です.
リボソーム救出機構は哺乳類の組織維持に重要な役割を果たします
ペロは表皮内の異なる幹細胞集団に特異的な効果を発揮する.
トランスレーション制御メカニズムをターゲットにすることで,組織ホメオスタシス障害の治療方法を提供することができます.

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