2 機能の細菌のタンパク質は,GDIの異位を Rab1の活性化と結びつける
Matthias P Machner1, Ralph R Isberg
1Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA 02111, USA.
まとめ
レジオネラ菌のタンパク質SidMは,Rab1.1のグアニンヌクレオチド交換因子 (GEF) とGDI置換因子 (GDF) の両方として作用する. この二重な活動は,宿主細胞の感染中にバクテリアの真空にRab1を勧誘する上で極めて重要です.
科学分野:
- 細胞生物学 細胞生物学
- 微生物学 微生物学とは
- 分子生物学は分子生物学である.
背景:
- ラブ・グアナシン・トリフォスファタゼ (GTPases) は,真核細胞における膀の密輸の重要な調節体である.
- 不活性なRab GTPasesは,GDP分裂阻害剤 (GDI) によって細胞溶液に隔離されます.
- 特定の因子によるGDIのシフトは,グアニンヌクレオチド交換因子 (GEFs) によるRab GTPase活性化に不可欠と考えられています.
研究 の 目的:
- レジオネラ肺 SidMタンパク質の機能を調査する.
- SidMがGDI-異動因子 (GDF) アクティビティを持っているかどうかを判断します.
- 宿主細胞の感染中にRab1の徴募におけるSidMの役割を明らかにする.
主な方法:
- 浄化されたSidMとRab1.1を用いたインビトロアッセイ.
- リポソーム結合測定は,膜関連性を評価するために行われます.
- 宿主細胞のレジオネラを含む真空にRab1の誘導を分析した.
主要な成果:
- SidMは,GEFとRab1のGDFの両方として機能し,二重の活動を実証しました.
- SidMによってGDIから放出されたRab1は,脂質体膜に挿入された.
- SidMのGDF活動は,ラブ1をレジオネラを含む真空孔に誘導するために不可欠でした.
結論:
- SidMという単一のタンパク質は,GEFとGDFの両方の活動を持つことができます.
- SidMのGDF機能は,GDIに縛られたプールからRab1の採用を調整するために不可欠です.
- この研究は,細菌の病原生殖の間にRab GTPaseの局所化を調節するための新しいメカニズムを明らかにしています.
関連する概念動画
Rab Proteins
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...
Rab Cascades
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.
Small GTPases - Ras and Rho
Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
IP3/DAG Signaling Pathway
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and produces two-second...
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...


