APCはRNA結合タンパク質であり,そのインタラクトームは神経発達と微小管の組み立てとのリンクを提供します
Nicolas Preitner1, Jie Quan1, Dan W Nowakowski1
1Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Cell
|July 19, 2014
まとめ
Adenomatous polyposis coli (APC) のタンパク質は,β2B-チューブリンmRNAを含むRNAに結合する. この相互作用は,タンパク質合成をダイナミックなマイクロチューブルに局所化することによって,ニューロン移動に不可欠です.
科学分野:
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
- 神経科学は神経科学である.
背景:
- Adenomatous polyposis coli (APC) は,様々な細胞プロセスに関与する重要な微小管関連タンパク質です.
- RNAの局所化におけるAPCの役割とその機能的意義は完全に理解されていません.
研究 の 目的:
- APCのRNA結合能力を調査する.
- APCのRNAインタラクトームを特定し,細胞プロセス,特にニューロン移動におけるその機能的影響を理解する.
主な方法:
- APC結合RNAを識別するために,クロスリンク免疫プレシピテーション (HITS-CLIP) によって分離されたRNAの高通量配列化.
- 遺伝子発現と細胞機能に対するAPC-RNA相互作用の影響を評価するためのインビトロおよびインビボ実験.
主要な成果:
- APCは,マイクロチューブル組織,細胞運動性,癌,神経疾患における機能のために濃縮された有意なRNAインタラクトームを持つRNA結合タンパク質として特定されました.
- β2B-チューブリンmRNAは,APCの直接標的として特定され,APCは3' UTR.に結合する.
- APC-β2B-チューブリン相互作用の障害は,β2B-チューブリンmRNAの軸索の局所化と発現を阻害し,成長コンの周辺のダイナミックなマイクロチューブルを減少させ,ニューロン移動を阻害しました.
結論:
- APCは,機能的に関連したタンパク質とRNAネットワークを結合し,支架として機能します.
- APCは,成長コンのダイナミックなマイクロチューブルにmRNAを誘導することによって,β2B-チューブリンなどの独自のサブユニットの局所合成を促進し,マイクロチューブル調節のための自己組織化モデルを提案します.
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