Ras-membraneの相互作用の圧力調節とインターベシクル移転の圧力調節
Shobhna Kapoor1, Alexander Werkmüller, Roger S Goody
1Physical Chemistry I-Biophysical Chemistry, Faculty of Chemistry, TU Dortmund University, Otto-Hahn-Strasse 6, D-44227 Dortmund, Germany.
Journal of the American Chemical Society
|April 9, 2013
まとめ
高水圧 (HHP) は,細胞膜とのN-Rasタンパク質の相互作用に影響します. この研究は,圧力がN-Ras膜結合,解離,およびクラスタリングに影響することを明らかにし,機械感知における役割を示唆しています.
科学分野:
- バイオフィジックス 生物物理学
- 細胞生物学 細胞生物学
- 分子シグナリング
背景:
- プラズマ膜タンパク質は,高水圧 (HHP) のような機械的ストレスにさらされます.
- Rasのような小さなGTPasesは,圧力に敏感なシグナル伝達経路に関与しています.
- 生物学的プロセスに対する機械的な力の正確な影響は,ほとんど不明のままです.
研究 の 目的:
- HHPがN-Ras.の膜結合,解離,移転に及ぼす影響を調査する.
- 圧力下でのN-Ras膜相互作用の運動パラメータと体積特性を決定する.
- 脂質シグナル分子のメカノセンサとしての可能性を探求する.
主な方法:
- フォースター共振エネルギー転送 (FRET) ベースの測定法を使用しました.
- N-Ras膜プロセスの定量化された運動パラメータと体積特性.
- 異なる脂質膜の組成と組織におけるN-Rasの振る舞いを調べました.
主要な成果:
- HHPは,N-Ras.の膜結合を促進する.
- N-Ras解離に対するHHPの影響は,脂質膜の特性によって異なります.
- HHPは,特に異質な膜におけるN-Rasのクラスタリングを強化する.
結論:
- N-Rasのような膜関連タンパク質は,機械的圧力に対して敏感である.
- 脂質シグナル分子は機械センサーとして作用し,機械的刺激を化学信号に変換する.
- 発見は,深海のような極端な環境での圧力調節信号への洞察を提供します.
関連する概念動画
02:38The Ras Gene
The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
Ras is a superfamily...
Ras is a superfamily...
01:24Small 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:
01:14Rab 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...
01:26Membrane Fluidity
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
01:25Rab 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.
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...