膜の密輸 膜の密輸 核酸二酸化リン酸キナーゼは,膜改造のためのGTPを持つダイナミン超家族タンパク質を燃料にしています
Mathieu Boissan1, Guillaume Montagnac2, Qinfang Shen3
1Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. Université Pierre et Marie Curie, University Paris 06, Paris, France. Saint-Antoine Research Center, INSERM UMR-S 938, Paris, France. mathieu.boissan@inserm.fr philippe.chavrier@curie.fr.
まとめ
核酸二酸化リン酸キナーゼ (NDPKs) は,ダイナミンモーターにグアノシン三酸化リン酸 (GTP) を供給し,これは内分細胞症とミトコンドリア融合における膜改造に不可欠である. この相互作用は,これらの重要な細胞プロセスのための効率的なエネルギー利用を保証します.
科学分野:
- 細胞生物学 細胞生物学
- 分子モーターは分子モーターです.
- メンブラン取引 メンブラン取引
背景:
- ダイナミン超族のタンパク質は,GTPに依存した分子モーターで,内分細胞症などの細胞プロセス中の膜改造に不可欠です.
- 核酸二酸化リン酸キナーゼ (NDPKs) は,ATPを用いてGDPからGTPを合成する酵素である.
- ダイナミンの機能を調節するNDPKの特定の役割と,膜動力学への関与は完全に理解されていません.
研究 の 目的:
- ダイナミン媒介の膜改造イベントにおけるNDPKs,特にNM23-H1/H2およびNM23-H4の役割を調査する.
- NDPKsがダイナミン超家族タンパク質と相互作用し,それを調節するメカニズムを解明する.
- NDPKの活性がエンドサイトーシスとミトコンドリア動力学に及ぼす機能的影響を決定する.
主な方法:
- NM23-H1/H2およびNM23-H4の発現を減らすために小さな干渉RNA (siRNA) を使用したノックダウン研究.
- 免疫光顕微鏡で,NDPKsとダイナミンタンパク質の局所性を評価する.
- GTP負荷と膜分裂を研究するために,精製されたタンパク質を用いたインビトロアッセイ.
- NDPKサイレンシング後のミトコンドリア形態の分析.
主要な成果:
- NM23-H1/H2のノックダウンにより,ダイナミン媒介性エンドサイトーシスが抑制され,ダイナミンのGTP負荷が低下しました.
- NM23-H1/H2タンパク質はクラスリンで覆われた穴に局所化し,ダイナミンと相互作用し,GTP結合と管分裂を促した.
- ミトコンドリア特異的なNM23-H4がOPA1とコロカライズされ,そのサイレンスがミトコンドリアの断片化につながり,ミトコンドリア融合における役割を示している.
結論:
- NM23-H1/H2およびNM23-H4を含むNDPKは,ダイナミン超家族タンパク質 (ダイナミンおよびOPA1) と直接相互作用する.
- NDPKはダイナミンのGTP供給者として機能し,膜改造のための熱力学的効率を高めます.
- この研究では,NDPKsとダイナミンの間の重要な機能的なリンクが,エンドサイトーシスやミトコンドリアのダイナミクスなどの基本的な細胞過程を調節する上で明らかにされています.
関連する概念動画
Pinching-off of Coated Vesicles
3.1K
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...
3.1K
The Movement of Organelles and Vesicles
5.4K
In eukaryotic cells, cytoskeletal filaments such as actin, microtubules, and intermediate filaments form a mesh-like cytoskeletal network. These filaments serve as tracks for transporting cellular cargo. Specialized motor proteins use the chemical energy stored in adenosine triphosphate (ATP) for this transport. During interphase, microtubules are polarized, with the plus-end towards the cell periphery and the minus-end towards the cell center. Two microtubule-associated motor proteins,...
5.4K
Coat Assembly and GTPases
3.5K
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...
3.5K
Rab Proteins
4.0K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
4.0K
Rab Cascades
2.8K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.8K
SNAREs and Membrane Fusion
10.3K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
10.3K


