压力调节的拉斯膜相互作用和间转移的压力调节
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
概括
高水静压 (HHP) 影响N-Ras蛋白与细胞膜的相互作用. 这项研究揭示了压力对N-Ras膜协会,解离和聚类的影响,这表明它在机械感知中发挥了作用.
科学领域:
- 生物物理学的生物物理.
- 细胞生物学 细胞生物学
- 分子信号传输的方法
背景情况:
- 等离子体膜蛋白暴露于机械应力,如高水静压 (HHP).
- 像Ras这样的小GTPase参与了对压力敏感的信号通路.
- 机械力对生物过程的确切影响仍然在很大程度上是未知的.
研究的目的:
- 研究HHP对N-Ras.的膜结合,解离和转移的影响.
- 为了确定压力下的N-Ras膜相互作用的动力参数和体积特性.
- 探索脂质信号分子作为机械传感器的潜力.
主要方法:
- 使用了基于弗斯特尔共振能量转移 (FRET) 的测定方法.
- 量化N-Ras膜工艺的动力参数和体积特性.
- 检查了N-Ras在不同脂质膜组成和组织中的行为.
主要成果:
- HHP促进了N-Ras.的膜结合.
- HHP对N-Ras解离的作用因脂质膜性质而异.
- 高平增强N-Ras聚类,特别是在异质膜中.
结论:
- 像N-Ras这样的膜相关蛋白对机械压力敏感.
- 脂质信号分子可以充当机械传感器,将机械刺激转化为化学信号.
- 研究结果提供了关于压力调节信号在极端环境,如深海的见解.
相关概念视频
The 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...
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:
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...
Membrane 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...
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.
MAPK 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...


