低オスモティック性のストレスが,アヌプロイドの一般的な細胞欠陥の基礎となっている

Hung-Ji Tsai¹, Anjali R Nelliat^1,2, Mohammad Ikbal Choudhury³

¹Center for Cell Dynamics, Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Nature

|May 10, 2019

まとめ

アヌプロイド性,または異常な染色体数は細胞にヒポオスモティックなストレスとプラズマ膜の欠陥を引き起こしますこれは栄養素の吸収と細胞サイズに影響しイーストとヒトの細胞の両方に影響を与えます

科学分野:

細胞生物学
遺伝学
分子生物学

背景:

染色体数の異常が特徴でがんや先天性欠陥などの病気と関連しています
異なるアヌプロイドは独特の遺伝子発現と表型プロフィールを引き起こしますが,一般的な細胞欠陥は十分に理解されていません.

研究の目的:

アヌプロイド症に関連した一般的な細胞欠陥と遺伝子発現シグネチャーを特定する.
モデル生物とヒトの細胞におけるアヌプロイドの機能的影響を調査する.

主な方法:

カリオタイプ特異的な影響を軽減する多種多様なアヌプロイドのトランスクリプトーム変化を平均するために,発芽酵母における戦略を活用した.
プロテオームの不均衡を分析し,プロイディ細胞サイズ関係を予測するために熱力学モデルを使用した.
アヌプロイド細胞の依存性を明らかにするために全ゲノムスクリーニングを行いました.

主要な成果:

ハイポスモティック・ストレスを示す常見のアネウプロイド性遺伝子発現のサインを特定した
プラズマ膜のストレスが増加し,アヌプロイド酵母細胞の内細胞分裂が低下し,アヌプロイド細胞のヒト細胞にも存在している.
熱力学モデリングは,プロテオームの不均衡の結果として低オスモティック型のストレスを確認し,観察されたプロイディ細胞サイズ相関を予測した.
栄養媒体のユビキチン媒介の内細胞循環にアヌプロイド細胞の依存性を発見した.

結論:

アヌプロイド症は通常,低オスモスのようなストレスとプラズマ膜の欠陥を誘発し,エンドサイトーシスと栄養素ホメオスタシスに影響を与えます.
アヌプロイド性によるプロテオームの不均衡はこれらの細胞欠陥の根本的な要因です
アヌプロイド細胞は栄養媒体の循環経路に特異的な脆弱性を表し,栄養の不均衡を悪化させる.

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