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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...

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...

Maturation of Endosomes

Maturation of Endosomes

The early endosome containing internalized molecules matures through transformations in its location, morphology, intraluminal pH, and membrane protein composition. Together, these changes result in a more acidic late endosome that contains multiple intraluminal vesicles; therefore, the late endosome is also called a multivesicular body (MVB).
Changes in location
The maturing endosome moves along microtubules from the periphery of the cell towards the perinuclear region. This movement of the...

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...

Export of Misfolded Proteins out of the ER

Export of Misfolded Proteins out of the ER

After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...

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Related Experiment Video

Updated: Feb 28, 2026

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

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Published on: February 12, 2022

Rubicon controls endosome maturation as a Rab7 effector.

Qiming Sun¹, Wiebke Westphal, Kwun Ngok Wong

¹Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.

Proceedings of the National Academy of Sciences of the United States of America

|October 27, 2010

Summary

Rubicon, a Rab7 effector, regulates endosome maturation by controlling UVRAG interactions. This mechanism ensures proper progression of the endocytic pathway.

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Area of Science:

Cell Biology
Molecular Biology
Endocytosis

Background:

Rab7 activation is crucial for endosome maturation, requiring PI3KC3 and GTPase regulators.
The precise molecular mechanism of Rab7 activation and endosome maturation remains unclear.

Purpose of the Study:

To elucidate the molecular mechanism of Rab7 activation and its role in endosome maturation.
To investigate the function of Rubicon in the PI3KC3 complex and its interaction with Rab7 and UVRAG.

Main Methods:

Biochemical assays to study protein interactions.
Analysis of Rab7 guanine nucleotide exchange activity.
Endocytosis assays to assess endosome maturation.

Main Results:

Rubicon, a PI3KC3 complex component, inhibits endosome maturation by sequestering UVRAG from C-VPS/HOPS.
Active GTP-bound Rab7 competes with Rubicon, releasing UVRAG to activate C-VPS/HOPS.
This interaction forms a feed-forward loop, amplifying GTP-bound Rab7 and stimulating endosome maturation.

Conclusions:

Rubicon acts as a novel Rab7 effector, modulating endosome maturation.
The Rubicon-UVRAG-C-VPS/HOPS interaction is critical for regulating Rab7 activity and endocytic pathway progression.