Pressure modulation of Ras-membrane interactions and intervesicle transfer
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
Summary
High hydrostatic pressure (HHP) affects N-Ras protein interactions with cell membranes. This study reveals pressure influences N-Ras membrane association, dissociation, and clustering, suggesting a role in mechanosensing.
Area of Science:
- Biophysics
- Cell Biology
- Molecular Signaling
Background:
- Plasma membrane proteins are exposed to mechanical stresses like high hydrostatic pressure (HHP).
- Small GTPases, such as Ras, are involved in pressure-sensitive signaling pathways.
- The precise impact of mechanical forces on biological processes remains largely unknown.
Purpose of the Study:
- To investigate the effects of HHP on the membrane association, dissociation, and transfer of N-Ras.
- To determine kinetic parameters and volumetric properties of N-Ras membrane interactions under pressure.
- To explore the potential of lipidated signaling molecules as mechanosensors.
Main Methods:
- Utilized a Förster Resonance Energy Transfer (FRET)-based assay.
- Quantified kinetic parameters and volumetric properties of N-Ras membrane processes.
- Examined N-Ras behavior in different lipid membrane compositions and organizations.
Main Results:
- HHP promotes the membrane association of N-Ras.
- HHP's effect on N-Ras dissociation varies with lipid membrane properties.
- HHP enhances N-Ras clustering, particularly in heterogeneous membranes.
Conclusions:
- Membrane-associated proteins like N-Ras are sensitive to mechanical pressure.
- Lipidated signaling molecules may act as mechanosensors, converting mechanical stimuli into chemical signals.
- Findings offer insights into pressure-regulated signaling in extreme environments like the deep sea.
More Related Videos
Related Concept Videos
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...


