ドレーパー依存性膠質ファゴサイト活性は,SrcおよびSykファミリーキナーゼシグナル伝達によって媒介されます
Jennifer S Ziegenfuss1, Romi Biswas, Michelle A Avery
1Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605-2324, USA.
Nature
|April 25, 2008
まとめ
ドロソフィラのドレーパー受容体の経路は,細胞残骸とアポプトシス細胞がグリアル細胞に飲み込まれるのを促進する. この古代のシグナリングカスケードはチロシンキナーゼを含み,種間の細胞クリアランスの保存されたメカニズムを明らかにしています.
科学分野:
- 細胞生物学 細胞生物学
- 神経科学は神経科学である.
- 発達生物学 発達生物学とは
背景:
- アポプトティック細胞のファゴサイトーシスは,無脊椎動物から哺乳類まで保存されているプロセスです.
- CED-1/Draper経路は,細胞の残骸や変性性軸索を含む様々な形態の"変性自己"をクリアするのに不可欠です.
- ドレーパー媒介ファゴサイトーシスの分子メカニズムを理解することは,細胞クリアランスを理解するための鍵です.
研究 の 目的:
- ドロソフィラドレーパー受容体の分子プレーヤーとシグナリングカスケードを明らかにする.
- 軸索破片および神経死体のドラパー媒介性ファゴサイトーシスにおけるチロシンキナーゼの役割を調査する.
- ドレーパー信号伝達経路と哺乳類の免疫受容体信号伝達を比較するために.
主な方法:
- Draper,Shark,Src42A.との間のタンパク質相互作用を決定する生化学的分析.
- ドロソフィラにおけるインビボ研究で,ドラパー媒介信号伝達のためのサメとSrc42Aの必要性を評価する.
- ドレーパーリン酸化と,切断されたアクソンへのグリア細胞の徴募の分析.
主要な成果:
- タイロシンキナーゼであるドロソフィラ・シャークは,免疫受容体タイロシンベースの活性化モチーフ (ITAM) を通して,ドレーパーに直接結合する.
- サメの活動は,ドレーパー媒介による軸索への状膜の徴集と,破片の細胞化に不可欠である.
- SrcファミリーキナーゼSrc42Aは,ドレーパーリン酸化を促進し,膠質ファゴサイト機能に不可欠です.
結論:
- ドレーパーへのリガンド結合は,Src42A依存ドレーパーリン酸化,サメ結合,経路活性化を含むシグナリングカスケードを開始する.
- Draper-Src42A-Sharkの相互作用は,哺乳類の免疫受容体-SFK-Sykの信号伝達経路を反映しています.
- ドレイパーは古代の免疫受容体として機能し,ITAM-ドメイン-SFK-Sykカスケードを使用して,改変した自己のファゴシトーシスを行う.
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