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Rab Cascades

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.

Rab Proteins

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...

Small GTPases - Ras and Rho

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:

Coat Assembly and GTPases

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...

GTPases and their Regulation

GTPases and their Regulation

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, also known...

GTPases and their Regulation

GTPases and their Regulation

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, also known...

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Related Experiment Video

Updated: Jul 8, 2026

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

The Rab GEF VINE couples phosphatase recruitment to GAP-mediated Rab5 inactivation.

Mia S Frier^1,2, Shawn P Shortill^1,2, Michael Davey²

¹Department of Medical Genetics, University of British Columbia, Vancouver, Canada.

The Journal of Cell Biology

|July 7, 2026

Summary

This summary is machine-generated.

The VINE complex, a guanine nucleotide exchange factor (GEF), unexpectedly inactivates Rab5 signaling by recruiting a phosphatase. This finding reveals a novel mechanism for fine-tuning endosomal trafficking and maturation.

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Last Updated: Jul 8, 2026

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Rab10 Phosphorylation Detection by LRRK2 Activity Using SDS-PAGE with a Phosphate-binding Tag

Published on: December 14, 2017

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

Affinity Precipitation of Active Rho-GEFs Using a GST-tagged Mutant Rho Protein (GST-RhoA(G17A)) from Epithelial Cell Lysates

Published on: March 31, 2012

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

Area of Science:

Cell Biology
Molecular Biology
Biochemistry

Background:

Rab5 GTPases regulate endosomal trafficking and membrane identity.
VPS9-family GEFs activate Rab proteins, while GAPs inactivate them.

Purpose of the Study:

To investigate the role of the yeast VPS9-family GEF complex VINE in Rab5 homolog Vps21 regulation.
To elucidate the mechanism by which VINE influences Vps21 activity.

Main Methods:

Genome-wide proximity screening
Predictive modeling
Targeted mutagenesis
In vivo assays

Main Results:

VINE recruits the protein phosphatase Glc7 via its Vrl1 subunit.
This recruits Glc7 to dephosphorylate Kxd1, enhancing its interaction with the Vps21-specific GAP Msb3.
This accelerates GAP-mediated Vps21 inactivation, limiting Rab signaling.

Conclusions:

VINE acts as a GEF complex that limits endosomal Rab signaling.
A novel mechanism integrating positive and negative Rab regulation is revealed.
This provides insight into the fine-tuning of Rab5 signaling in endosomal trafficking and maturation.