バシジンは,Plasmodium falciparumによる赤血球の侵入に不可欠な受容体です
Cécile Crosnier1, Leyla Y Bustamante, S Josefin Bartholdson
1Cell Surface Signalling Laboratory, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1HH, UK.
Nature
|November 15, 2011
まとめ
科学者は,Plasmodium falciparumマラリア寄生虫は,すべての株で赤血球の侵入のために,ベースギン受容体とPfRh5リガンドを必要としていることを発見しました. この重要な相互作用は,新しい抗マラリア治療のための有望なターゲットを提供します.
科学分野:
- マラリア学 マラリア学
- 寄生虫学とは,寄生虫学である.
- 分子および細胞生物学
背景:
- プラズモジアム・ファルシパラムによる赤血球の侵入は,マラリアの病原性にとって極めて重要です.
- 既存の知識は,異なる寄生虫株によって使用される複数の冗長な侵入経路を示しています.
- すべてのP. falciparum株において,単一の受容体-リガンド相互作用が不可欠であるとは認められていない.
研究 の 目的:
- すべての試験株において,P. falciparumの赤血球侵入に不可欠な受容体-リガンドペアを特定する.
- マラリア寄生虫の侵入機構におけるバシジンとPfRh5の役割を調査する.
- マラリアに対する新たな治療目標の可能性を調査する.
主な方法:
- 寄生虫リガンドの受容体を特定するために,赤血球タンパク質の体系的なスクリーニング.
- 溶性バシギン,バシギンノックダウン,および抗バシギン抗体が侵入を抑制するために使用された機能検査.
- 変異したベースリン結合親和性を有するOK (((a-) エリトロサイトにおける侵入効率の分析.
主要な成果:
- P. falciparum のリガンド PfRh5.5 の必須受容体として,バシジン (OK 血液型抗原) を特定しました.
- 溶性バシギン,バシギンノックダウン,および抗バシギン抗体によって,テストされたすべての株で,赤血球の侵入を強力に抑制することが実証されています.
- 弱いPfRh5結合により,OK(a-) 赤血球における侵入効率の低下が観察されました.
結論:
- PfRh5-basiginの相互作用は,P. falciparumの赤血球侵入のためのクロスストレインの重要な経路です.
- この保存された受容体-リガンドペアは,広範囲の抗マラリア薬の開発に非常に有望な標的を代表しています.
- この相互作用をターゲットにすることで,冗長な侵入経路に関連する抵抗機構を克服することができます.
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