Related Experiment Video
Updated: Dec 26, 2025
10:27
Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
Published on: March 9, 2012
11.2K
Stochastic activation and bistability in a Rab GTPase regulatory network
Urban Bezeljak1, Hrushikesh Loya2, Beata Kaczmarek1
1Institute of Science and Technology Austria, 3400 Klosterneuburg, Austria.
Summary
This study reveals how Rab5 GTPase networks create traveling waves of activation, controlling cell vesicle transport. Understanding these collective switching dynamics is key to cell organization.
Area of Science:
- Cell Biology
- Biochemistry
- Systems Biology
Background:
- The eukaryotic endomembrane system relies on Rab GTPases for regulated vesicle trafficking.
- Individual Rab protein activation is understood, but network-level control of cellular activity patterns remains unclear.
Purpose of the Study:
- To investigate the regulatory mechanisms governing Rab5 activation dynamics within a minimal network.
- To elucidate how molecular interactions generate spatiotemporal control of Rab5 activity.
Main Methods:
- In vitro reconstitution of a minimal Rab5 activation network.
- Computational modeling to analyze network behavior.
- Experimental validation of predicted network properties.
Main Results:
- Identified positive feedback and bistable collective switching in the Rab5 network.
- Demonstrated intrinsic stochasticity in switching near critical points.
- Showed that controlling inactive Rab5 populations shapes network response.
- Observed traveling waves of Rab5 activation spreading across membranes.
Conclusions:
- Biochemical signaling networks, through collective switching and nonequilibrium properties, dictate the spatiotemporal organization of cellular processes like vesicle trafficking.
- This work provides a framework for understanding how complex cellular functions emerge from simple molecular interactions.
Related Concept Videos
01:25Rab Cascades
3.3K
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.
3.3K
01:14Rab Proteins
4.9K
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...
4.9K
01:22Activation and Inactivation of G Proteins
10.4K
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...
10.4K
01:24Small GTPases - Ras and Rho
5.1K
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:
5.1K
02:14GTPases and their Regulation
9.6K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
9.6K
02:14GTPases and their Regulation
2.7K
2.7K