Related Experiment Video
Updated: Aug 9, 2025

16:01
Investigating Mast Cell Secretory Granules; from Biosynthesis to Exocytosis
Published on: January 26, 2015
13.2K
Exploring the consequences of redirecting an exocytic Rab onto endocytic vesicles.
Xia Li1, Dongmei Liu1, Eric Griffis2
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, California, United States.
Biorxiv : the Preprint Server for Biology
|February 17, 2023
Summary
Cells can tolerate misdirected Rab GTPases, crucial regulators of vesicular transport. This study shows that even when exocytic Rabs are redirected to endocytic vesicles, cellular growth and protein secretion remain largely unaffected.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Bidirectional vesicular traffic is essential for cellular function, connecting exocytic and endocytic pathways.
- Rab GTPases are key regulators, with distinct Rabs marking anterograde and retrograde vesicles to ensure directional transport.
Approach:
- Engineered a fusion protein combining the Sec4 GEF catalytic domain (Sec2) with the CUE domain of Vps9.
- Investigated the localization and function of this construct, which redirects the exocytic Rab Sec4 to endocytic vesicles.
Key Points:
- The engineered construct localized to puncta dependent on ubiquitin binding, recruiting Sec4 and its effectors.
- These puncta contained clusters of vesicles, with dynamic traffic observed via FRAP analysis.
- Cells expressing the construct exhibited near-normal growth and protein secretion despite Rab misdirection.
Conclusions:
- Vesicular transport is remarkably tolerant of Rab misdirection.
- While Rabs are critical, their precise localization may be less stringent than previously thought for basic cellular functions.
Related Concept Videos
Recycling Endosomes and Transcytosis
2.7K
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...
2.7K
Rab 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
Rab Proteins
4.0K
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...
4.0K
The Early Endosome: Endocytosis of Transferrin
3.4K
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...
3.4K
Receptor-mediated Endocytosis
6.2K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
6.2K
SNAREs and Membrane Fusion
11.0K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
11.0K

