アクチンの成熟にはACTMAP/C19orf54プロテアゼが必要です

Peter Haahr^1,2, Ricardo A Galli³, Lisa G van den Hengel^1,4

¹Division of Biochemistry, Netherlands Cancer Institute, 1066CX Amsterdam, Netherlands.

Science (New York, N.Y.)

|September 29, 2022

まとめ

研究者らは,ACTMAPを翻訳後のメチオニンを除去することによってアクチンを成熟させる酵素と特定しました. この欠乏は未熟なアクチン,筋肉の繊維の短縮,およびマウスにおける筋病の特徴につながる.

科学分野:

生物化学
分子生物学
細胞生物学

背景:

タンパク質合成は通常,メチオニンで始まり,通常はトランスレーションで除去されます.
細胞質アクチンは,未知の酵素によってアセチル化メチオニンの除去を含むユニークな翻訳後の改変を経験する.

研究の目的:

アクチンの非正規の翻訳後の改変に責任のある酵素を特定する.
アクチン成熟におけるこの酵素のインビボ機能と筋肉生理におけるその役割を調査する.

主な方法:

遺伝子スクリーニングと生化学分析による酵素識別
特定された酵素を欠いたノックアウトマウスの生成と分析
ミュータントマウスにおける細胞骨格構造,アクチンフィラメント長さ,筋肉機能,および組織学的特徴の評価.

主要な成果:

ACTMAP (アクチン成熟プロテアゼ) と指定されたC19orf54は,アクチンからアセチルメチオニンを除去する酵素として特定されました.
ACTMAPの消去により,すべての組織に不成熟なアクチンが生じた.
ACTMAP欠乏したマウスの骨格筋は,サルコメリックアクチンフィラメントが短く,筋肉の機能が低下し,中心核の漸進的な蓄積がみられ,ミオパシーを示唆した.

結論:

ACTMAPは成熟した細胞質アクチンの生成に不可欠な酵素です.
ACTMAPは正常なアクチンフィラメントの長さと筋肉の機能を維持する上で重要な役割を果たします.
ACTMAPの欠乏は,アクチン関連のミオパシーにつながる.

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