PKCgammaは,xenopusの左から右の発達過程で,シンデカン-2の内側から外側へのシグナリングを調節する
Kenneth L Kramer1, Janet E Barnette, H Joseph Yost
1Center for Children, Huntsman Cancer Institute, Department of Oncological Sciences, University of Utah, Salt Lake City 84112, USA.
Cell
|January 1, 2003
まとめ
タンパク質キナーゼCガンマ (PKCgamma) は,右外皮細胞におけるシンデカン-2のリン酸化を制御し,左右 (LR) 発達の重要なステップである. このリン酸化は,発達初期における非対称的な遺伝子発現と臓器の指向に不可欠である.
科学分野:
- 発達生物学 発達生物学とは
- 細胞シグナル伝達 細胞信号伝達
- 分子生物学は分子生物学である.
背景:
- 膜経プロテオグリカンシンデカン-2は,左-右 (LR) 発達パターニングにおいて非自律的な役割を果たします.
- 遺伝子発現と臓器の指向を含む,シンデカン-2がLR非対称性を調節する正確な分子機構は,ほとんど不明のままである.
- LRの発達は,胚の発達初期に非対称なシグナリングを含む複雑なプロセスです.
研究 の 目的:
- 左-右 (LR) 発達中のシンデカン-2の調節におけるタンパク質キナーゼCガンマ (PKCgamma) の役割を調査する.
- シンデカン-2のリン酸化がLRの非対称遺伝子発現と臓器の指向に影響するメカニズムを解明する.
- 細胞と細胞の相互作用によって媒介されたLR発達の初期の分子イベントを特定する.
主な方法:
- 動物のキャップのエキスプラントを活用して,移住するメソデルマとエクトダーマ細胞の相互作用を研究しました.
- 右と左の皮膚外皮細胞におけるシンデカン-2のリン酸化状態を調査した.
- シンデカン-2リン酸化を媒介するPKCガマの役割を調べました.
- 正常なLR発達のために,リン酸化および非リン酸化シンデカン-2状態の必要性を評価した.
主要な成果:
- タンパク質キナーゼCガンマ (PKCgamma) が,特に右動物帽外皮細胞におけるシンデカン-2の細胞質ドメインのリン酸化を媒介することを示した.
- リン酸化シンデカン-2 (右細胞) と非リン酸化シンデカン-2 (左細胞) の両方が正常なLR発育に不可欠であることを示した.
- このエクトダーマ・メソダーマ細胞の接触とシンデカン-2のリン酸化は,モノシリアの出現に先立ち,ガストルーレーションの初期に起こることが確認されました.
- PKCgammaはシンデカン-2のリン酸化を調節し,隣接する細胞への内外シグナル伝達に影響を与えると結論付けました.
結論:
- PKCガマは,LR発達の初期に,右側外皮細胞におけるシンデカン-2のリン酸化の主要な調節体である.
- PKCgammaによって調節されるシンデカン-2のリン酸化状態は,LR非対称性を確立するために重要である.
- この研究は,LRパターニングにおけるシンデカン-2とPKCガマを含む早期の,細胞接触に依存するメカニズムを明らかにし,モノシリア形成のような既知の後の出来事に先立ちます.
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