FCHoタンパク質は,クラスリン媒介性エンドサイトーシスのニュクレエーターである
William Mike Henne1, Emmanuel Boucrot, Michael Meinecke
1Medical Research Council, Laboratory of Molecular Biology (MRC-LMB), Hills Road, Cambridge CB2 0QH, UK.
まとめ
鉄/Cip4ホモロジードメインのみのタンパク質1と2 (FCHo1/2) は,プラズマ膜を彫刻することでクラトリンで覆われた膀 (CCV) の芽生えを開始します. これらのタンパク質は,リガンドエンドサイトーシスと,真核細胞におけるシナプス胞のリサイクルに不可欠である.
科学分野:
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
- バイオケミストリー バイオケミストリー
背景:
- クラトリン媒介性内分細胞症 (CME) は,リガンドを細胞内に内化するのに極めて重要です.
- CMEは伝統的にクラトリンとアダプタタンパク質のクラスタリングから始まると考えられています.
- プラズマ膜でのCMEの発起の正確なメカニズムは,まだ完全に理解されていません.
研究 の 目的:
- CMEにおけるFer/Cip4ホモロジードメインのみのタンパク質1と2 (FCHo1/2) の役割を調査する.
- FCHo1/2タンパク質がクラトリンコーティングベジクル (CCV) 形成の開始に関与しているかどうかを判断する.
- FCHo1/2タンパク質がCCVの芽生えを調節する分子メカニズムを解明する.
主な方法:
- ユカリオット細胞におけるタンパク質の局所化と機能を研究する技術を用いた.
- 操作されたFCHo1/2発現レベルは,エンドサイトーシスへの影響を観察するために.
- FCHo1/2,スキャフォールドタンパク質,およびAP2複合体間のタンパク質とタンパク質の相互作用を調査した.
- CCV形成のためのFCHo F-BARドメイン活動の必要性を評価しました.
主要な成果:
- FCHo1/2タンパク質は,プラズマ膜のCCV芽生えに必要であり,CCV形成部位をマークします.
- FCHo1/2の発現レベルは,CCVの芽生えイベント,リガンド内分細胞症,シナプス膀のリサイクルと直接相関しています.
- FCHo1/2タンパク質は,プラズマ膜に結合し,eps15とインターセクチンを誘導し,その後AP2.2を誘導する.
- FCHo F-BARドメインの膜屈曲活動は,これらの機能に不可欠です.
結論:
- FCHo1/2タンパク質は,初期芽部部を形作ることで,CMEの発症に重要な役割を果たします.
- FCHo1/2タンパク質は,AP2の募集の前向きに作用し,クラスリン機構の組み立てを開始します.
- これらの発見は,クラスリン媒介性内分細胞症の開始のための新しいメカニズムを明らかにします.
関連する概念動画
Clathrin Coated Vesicles
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
Molecular Chaperones and Protein Folding
The native conformation of a protein is formed by interactions between the side chains of its constituent amino acids. When the amino acids cannot form these interactions, the protein cannot fold by itself and needs chaperones. Notably, chaperones do not relay any additional information required for the folding of polypeptides; the native conformation of a protein is determined solely by its amino acid sequence. Chaperones catalyze protein folding without being a part of the folded protein.
The...
The...
Pinching-off of Coated Vesicles
Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
Coat Assembly and GTPases
Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
COP Coated Vesicles
Membrane-enclosed structures called vesicles transport proteins and lipids across the cell. The vesicles derive their cargo from the plasma membrane, Golgi, ER, or endosome. Coated vesicles are spherical, protein-coated carriers with a 50–100 nm diameter that mediate bidirectional transport between the ER and the Golgi. The distribution of proteins between the ER and Golgi complex is dynamic and is maintained by different coated vesicles. Their formation is driven by the assembly of different...


