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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...

The Early Endosome: Endocytosis of Transferrin

The Early Endosome: Endocytosis of Transferrin

Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...

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...

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:

Recycling Endosomes and Transcytosis

Recycling Endosomes and Transcytosis

The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...

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Related Experiment Video

Updated: May 11, 2025

In Vitro Polymerization of F-actin on Early Endosomes

In Vitro Polymerization of F-actin on Early Endosomes

Published on: August 28, 2017

Identification of Rab GTPase-Activating Proteins Required for Tubular Endosome Formation.

Shumpei Nakashima¹, Mitsunori Fukuda¹

¹Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan.

Traffic (Copenhagen, Denmark)

|April 17, 2025

Summary

Researchers identified four GTPase-activating proteins (GAPs) that regulate tubular endosome formation. These Rab-GAPs, including TBC1D10B, are crucial for maintaining tubular endosome structure and cargo recycling.

Keywords:

GTPase‐activating protein (GAP)Rab22A Tre‐2/Bub2/Cdc16 (TBC) domain comprehensive screening membrane traffic small GTPase tubular endosome

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Last Updated: May 11, 2025

In Vitro Polymerization of F-actin on Early Endosomes

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Published on: August 28, 2017

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

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Published on: December 14, 2017

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

Published on: February 12, 2022

Area of Science:

Cell biology
Molecular and cell biology
Endocytosis and intracellular trafficking

Background:

Clathrin-independent endocytosis involves tubular endosomes for cargo recycling.
Rab small GTPases, like Rab22A, regulate tubular endosome structure and function.
Rab GTPase activity is modulated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs).

Purpose of the Study:

To identify Rab-GAPs involved in tubular endosome formation.
To investigate the role of specific Rab-GAPs in regulating Rab22A activity and tubular endosomes.

Main Methods:

Comprehensive screening of TBC/Rab-GAPs in HeLa cells.
Analysis of tubular endosome structures following knockdown or overexpression of Rab-GAPs.
Assessment of active Rab22A levels and Rab22A-positive early endosome size.

Main Results:

Four Rab-GAPs (TBC1D10B, TBC1D18, TBC1D22B, EVI5) were identified as regulators of tubular endosome formation.
Knockdown or overexpression of these Rab-GAPs impaired tubular endosome structures in a GAP-activity-dependent manner.
TBC1D10B was identified as a likely Rab22A-GAP, reducing active Rab22A and early endosome size.

Conclusions:

Rab-GAPs play a critical role in the formation and maintenance of tubular endosomes.
A balanced GTPase cycle, involving both GEFs and GAPs, is essential for tubular endosome regulation.
These findings identify novel regulators of endosomal trafficking and provide insights into Rab protein function.