フォスファディチルコリントランスロカゼ: mdr2遺伝子の生理学的役割
Cell
|July 1, 1994
まとめ
マウス mdr2 P-グリコタンパク質 (P-gp) は,酵母分泌小胞の脂質フリッパースとして機能する. この脂質トランスロカースの活動はATPに依存しており,phosphatidylcholineに特異的であり, mdr3 P-gpとは違います.
科学分野:
- バイオケミストリー バイオケミストリー
- 分子生物学は分子生物学である.
- 細胞生物学 細胞生物学
背景:
- P-グリコタンパク質 (P-gps) は,多剤耐性に関与するATP結合カセットトランスポーターである.
- 脂質輸送におけるそれらの役割,特に脂質トランスロカゼまたはフリッパゼとして,活発な研究分野です.
- P-gpの機能を理解することは,薬剤開発と細胞脂質ホメオスタシスにとって極めて重要です.
研究 の 目的:
- ネズミのmdr2およびmdr3 P-グリコタンパク質の脂質トランスロカゼ/フリッパゼ活性を調べる.
- ヘテロログなシステムにおける mdr2 と mdr3 P-gps の機能的差異を特徴づける.
- イーストの分泌膀における脂質非対称性を定量化するための測定法を開発し,利用する.
主な方法:
- マウスのmdr2およびmdr3遺伝子の発現は,酵母菌の変異性Sec6-4の分泌小胞 (SVs) に見られる.
- 光フォスファティディルコリン (PC) アナログアッセイの開発,膀バイレイヤの脂質分布を測定する.
- さまざまな条件 (時間,温度,ATP,Mg2+,阻害剤,調節器) の下で,SVsの内側へPCの転位を分析する.
主要な成果:
- 酵母 SVsにおけるMdr2発現は,時間および温度に依存した方法で,内部の小葉書へのフォスファディチルコリン (PC) 転位を著しく強化しました.
- Mdr3発現はPC分布に影響を与えず,Mdr2媒介効果の特異性を示した.
- mdr2媒介のPC転位はATPとMg2+に依存し,バナダートとベラパミルによって抑制されたが,コルチシンやビンブラスティンによって影響を受けなかった.
結論:
- マウス mdr2 P-グリコタンパク質は,酵母分泌小胞におけるフォスファディチルコリンのための脂質トランスロカゼ (フリッパゼ) として機能する.
- Mdr2は,mdr3とは異なる特定の脂質輸送活動を示す.
- FLIPPASEとしてのMDR2 P-gpの活動はATPに依存し,特定の阻害剤とヴェラパミルによって調節され,そのP-gp性質と一致しています.
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