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Updated: Jun 25, 2025

Visualization of Endoplasmic Reticulum Subdomains in Cultured Cells
Published on: February 18, 2014
Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases
Abstract:
Peripheral endoplasmic reticulum (ER) tubules move along microtubules to interact with various organelles through membrane contact sites (MCS). Traditionally, ER moves by either sliding along stable microtubules via molecular motors or attaching to the plus ends of dynamic microtubules through tip attachment complexes (TAC). A recently discovered third process, hitchhiking, involves motile vesicles pulling ER tubules along microtubules. Previous research showed that ER hitchhikes on Rab5- and Rab7-marked endosomes, but it is uncertain if other Rab-vesicles can do the same. In U2OS cells, we screened Rabs for their ability to cotransport with ER tubules and found that ER hitchhikes on post-Golgi vesicles marked by Rab6 (isoforms a and b). Rab6-ER hitchhiking occurs independently of ER-endolysosome contacts and TAC-mediated ER movement. Disrupting either Rab6 or the motility of Rab6-vesicles reduces overall ER movement. Conversely, relocating these vesicles to the cell periphery causes peripheral ER accumulation, indicating that Rab6-vesicle motility is crucial for a subset of ER movements. Proximal post-Golgi vesicles marked by TGN46 are involved in Rab6-ER hitchhiking, while other post-Golgi vesicles (Rabs 8/10/11/13/14) are not essential for ER movement. Our further analysis finds that ER to Golgi vesicles marked by Rab1 are also capable of driving a subset of ER movements. Taken together, our findings suggest that ER hitchhiking on Rab-vesicles is a significant mode of ER movement.
Significance Statement:
Peripheral endoplasmic reticulum tubules move on microtubules by either attaching to motors (cargo adaptor-mediated), dynamic microtubule-plus ends (tip attachment complexes) or motile vesicles (hitchhiking) but the prevalence of each mode is not clearPost-Golgi vesicles marked by Rab6/TGN46 and ER to Golgi vesicles marked by Rab1 drive ER movementsER hitchhiking on multiple classes of vesicles (endolysosomal, post-Golgi and ER to Golgi) marked by Rabs plays a prominent role in ER movement.
Insights
Peripheral endoplasmic reticulum (ER) tubules move via hitchhiking on Rab-vesicles. This study reveals ER hitchhiking on post-Golgi Rab6 vesicles and ER-to-Golgi Rab1 vesicles is crucial for ER movement.
Area of Science:
- Cell Biology
- Molecular Biology
- Organelle Dynamics
Background:
- Peripheral endoplasmic reticulum (ER) tubules interact with organelles via membrane contact sites.
- ER movement relies on molecular motors, microtubule plus ends, or vesicle hitchhiking.
Approach:
- Screened Rab proteins in U2OS cells to identify vesicles involved in ER hitchhiking.
- Investigated the role of Rab6-marked post-Golgi vesicles and Rab1-marked ER-to-Golgi vesicles in ER motility.
- Disrupted Rab6 or vesicle motility to assess impact on ER movement.
Key Points:
- ER hitchhikes on post-Golgi vesicles marked by Rab6 (isoforms a and b).
- Rab6-ER hitchhiking is independent of ER-endolysosome contacts and tip attachment complexes.
- Motility of Rab6-vesicles is essential for a subset of ER movements.
- ER-to-Golgi vesicles marked by Rab1 also drive ER movements.
Conclusions:
- Peripheral ER tubules utilize multiple mechanisms for movement, including hitchhiking on various Rab-vesicle classes.
- ER hitchhiking on Rab-vesicles represents a significant mode of ER transport.
- Post-Golgi Rab6/TGN46 and ER-to-Golgi Rab1 vesicles are key drivers of ER movement via hitchhiking.
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