Related Experiment Video
Updated: Sep 20, 2025
11:05
Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells
Published on: February 21, 2019
9.2K
Disruption of Retriever Function Impacts Retrograde Trafficking From Endosomes
Zebin Li1, Zhe Yang1, Rohan D Teasdale1
1School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Australia.
Cell Biology International
|May 29, 2025
Summary
The retriever complex is essential for efficient endosomal retrograde trafficking, a process distinct from retromer
Area of Science:
- Cell Biology
- Molecular Biology
- Protein Trafficking
Background:
- Endosomal sorting and packaging into endosomal-transport carriers (ETCs) direct protein delivery.
- Retromer complex mediates ETC formation for retrograde trafficking and recycling.
- The retriever complex, similar to retromer, recycles cargo but its retrograde role is unknown.
Purpose of the Study:
- Investigate the role of the retriever complex in endosomal retrograde trafficking.
- Compare the functions of retromer and retriever in protein sorting and ETC formation.
- Elucidate the distinct mechanisms of retrograde ETC initiation by these complexes.
Main Methods:
- Generated CRISPR-mediated retromer and retriever knockout (KO) A549 cell models.
- Confirmed retriever's role in Integrin β1 recycling.
- Utilized ETC redirection assays and cargo redistribution analysis.
Main Results:
- Retriever KO cells showed decreased retrograde trafficking of cation-independent mannose 6-phosphate receptor and TGN46.
- Golgin97 and Golgin245 tethered ETCs dependent on either retromer or retriever.
- Retriever recruitment to endosomes is dependent on retromer, suggesting distinct mechanisms.
Conclusions:
- Retriever is required for efficient endosomal retrograde trafficking.
- The mechanisms initiating retrograde ETC formation by retromer and retriever appear distinct.
- Retromer is required for WASH recruitment, but retriever is not.
Related Concept Videos
00:58Recycling Endosomes and Transcytosis
2.8K
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...
2.8K
01:32Export of Misfolded Proteins out of the ER
3.9K
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...
3.9K
01:45ER Retrieval Pathway
3.9K
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...
3.9K
01:28The Early Endosome: Endocytosis of Transferrin
3.5K
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...
3.5K
01:44Introduction to Membrane Traffic
7.4K
The ER, Golgi apparatus, endosomes, and lysosomes work in tandem to modify, sort, and package proteins and lipids. An integrated membrane trafficking network facilitates the back and forth shuttling of molecules within different organelles in the same cell or across the cell membrane.
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
The transport of soluble and membrane proteins is mediated by transport vesicles that collect cargo from one cellular compartment and deliver it to another by fusing with the target organelle membrane. The Rab...
7.4K
01:25Rab Cascades
2.7K
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.
2.7K