ヴァソヒビン/SVBPはニューロン分化を調節するチューブリンカルボキシペプチダース (TCP) である

Chrystelle Aillaud^1,2, Christophe Bosc^1,2, Leticia Peris^1,2

¹Grenoble Institut des Neurosciences (GIN), Université Grenoble Alpes, F-38000 Grenoble, France.

Science (New York, N.Y.)

|November 18, 2017

まとめ

ヴァソヒビン-SVBP複合体は,微小管の機能に不可欠なプロセスであるオキソシネーションの鍵となる酵素として特定されています. この発見は癌や発達障害などの病気に光を当てました

科学分野:

細胞生物学
分子生物学
神経科学

背景:

アルファチューブリンを逆転させるのは,微小管の動態と細胞機能に不可欠である.
オキシトシンの調節不良は,がん,脳疾患,心筋病など様々な疾患と関連しています.
チューブリンチロシンカルボキシペプチダゼ (TCP) の特定の酵素は特定されなかった.

研究の目的:

脳内の主要なチューブリンチロシンカルボキシペプチダース (TCP) を特定する.
特定されたTCPの酵素活性と生物学的役割を明らかにする.

主な方法:

化学プロテオミクスは強力な不可逆的阻害剤を使用します
微小管のカルボキシペプチダース活性を決定する生化学的測定
遺伝子ノックダウン実験を培養ニューロンとマウスモデルで

主要な成果:

ヴァソヒビン-1 (VASH1) と小さなヴァソヒビン結合タンパク質 (SVBP) 複合体は,主要な脳TCPとして特定されました.
VASH1/ SVBPおよびVASH2/ SVBP複合体は,マイクロチューブルに特異的なTyr/ Pheカルボキシペプチダース活性を示した.
ヴァソヒビンまたはSVBPのノックダウンは,オキシトシン化されたアルファチューブリンを減少させ,神経細胞の分化および移動を阻害しました.

結論:

ヴァソヒビン/SVBP複合体は,長らく求められてきたTCP酵素で,オキシトシン化に責任があります.
この酵素複合体は微小管の調節と神経細胞の発達に重要な役割を果たします
この発見は,オキシトシネーションの欠陥に関連した疾患の基礎となる分子メカニズムについての洞察を提供します.

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