プロトカデリンは,哺乳類の神経系におけるデンドリット自己回避を媒介する
Julie L Lefebvre1, Dimitar Kostadinov, Weisheng V Chen
1Center for Brain Science and Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature
|July 31, 2012
まとめ
クラスター化されたプロトカデリン (Pcdhs) は,神経細胞が自己分岐を回避し,自己細胞と非自己細胞を区別することを可能にします. これにより,適切な神経回路の形成と機能が保証されます.
科学分野:
- 神経科学は神経科学である.
- 発達生物学 発達生物学について
- 分子生物学は分子生物学である.
背景:
- ニューロンの樹状樹木化は,同じニューロンの枝が互いに排斥する自己回避によってパターン化されています.
- 自己回避は,ニューロンの領域を完全にカバーし,ギャップや重複を最小限に抑えることを保証します.
- 自己回避を示す一部のニューロンは,同じサブタイプの他のニューロンと相互作用し,自己/非自己の差別を示唆します.
研究 の 目的:
- 群集したプロトカデリン (Pcdhs) がデンドリット自己回避と自己/非自己差別における役割を調査する.
- Pcdhsがニューロンの配線を調節する分子機構を解明する.
主な方法:
- ネズミの網膜のスターバーストアマクリン細胞 (SAC) と小脳パルキンジェ細胞におけるクラスターされたプロトカデリンガンマ (Pcdhg) 遺伝子の遺伝子解析.
- 遺伝子の消去と同形態の置換を含む機能的研究で, dendritic 自己回避への影響を評価する.
- ニューロンの発達中のPCdhgタンパク質の細胞自律機能の調査.
主要な成果:
- Pcdhg遺伝子の削除は,SACとPurkinje細胞のデンドリット自己回避を妨げました.
- Pcdhgタンパク質は細胞自律的に作用し,22個のPcdhgタンパク質を単一の同型で置き換えることで,自己回避が回復した.
- すべてのSACで単一のPcdhgイソフォームを表現すると,隣接するSACのデンドライト間の相互作用 (異性ニューロン相互作用) が減少します.
結論:
- 兄弟ニューライトの間のホモフィリックPcdhg相互作用 (同ニューロン相互作用) は排斥信号を生成し, dendritic自己回避につながります.
- ヘテロニューロン相互作用は,デンドライトがPcdhgタンパク質のマッチングセットを共有しない限り許可されているため,自己/非自己の差別が達成されます.
- 脊椎動物のPcdhsと昆虫のDscam1は,シーケンスホモロジーを欠くにもかかわらず,神経細胞の自己回避と自己/非自己の差別のために同様の戦略を採用しています.
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