Related Experiment Video
Updated: Dec 29, 2025
08:51
The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking
Published on: February 12, 2022
3.9K
FERARI is required for Rab11-dependent endocytic recycling
Jachen A Solinger1, Harun-Or Rashid1, Cristina Prescianotto-Baschong1
1Biozentrum, University of Basel, Basel, Switzerland.
Nature Cell Biology
|January 29, 2020
Summary
Researchers discovered a new protein complex, FERARI, crucial for endosomal transport. FERARI coordinates membrane fusion and fission, ensuring proteins are correctly recycled within cells.
Area of Science:
- Cell Biology
- Molecular Biology
- Cellular Trafficking
Background:
- Endosomal transport is vital for cellular organization, compartmentalization, and communication.
- Sorting endosomes act as key hubs, directing protein fate towards recycling, secretion, or degradation.
- Efficient endosomal organization relies on membrane-tethering factors coordinating Rab GTPase activity and membrane fusion.
Purpose of the Study:
- To identify and characterize conserved tethering platforms involved in Rab11 recycling pathways at sorting endosomes.
- To elucidate the molecular composition and function of this novel platform, termed FERARI (factors for endosome recycling and Rab interactions).
Main Methods:
- Proteomic analysis to identify components of the tethering platform.
- Biochemical assays to study protein-protein interactions and functional roles.
- Cellular imaging to visualize the localization and activity of FERARI components.
Main Results:
- A conserved tethering platform, FERARI, was identified in Rab11 recycling pathways at sorting endosomes.
- FERARI comprises Rab11FIP5, rabenosyn-5/RABS-5 (Rab-binding module), VPS45, and VIPAS39 (SNARE-interacting module).
- Unexpectedly, the membrane fission protein EHD1 was also identified as a FERARI component, suggesting a combined fusion-fission role.
Conclusions:
- FERARI integrates membrane fusion (via VPS45) and membrane fission (via EHD1) activities on SNX-1-positive endosomal membranes.
- This coordinated fusion and fission mechanism, proposed as a 'kiss-and-run' process, facilitates cargo movement into endosomal recycling pathways.
Related Concept Videos
00:58Recycling Endosomes and Transcytosis
3.4K
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...
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...
3.4K
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
01:28The Early Endosome: Endocytosis of Transferrin
4.6K
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...
4.6K
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
01:45ER Retrieval Pathway
4.6K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
4.6K
01:33Coat Assembly and GTPases
4.2K
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...
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...
4.2K