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Movement of the endoplasmic reticulum is driven by multiple classes of vesicles marked by Rab-GTPases

Allison Langley1,2, Sarah Abeling-Wang2, Erinn Wagner2

  • 1Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, VT 05405.

Molecular Biology of the Cell
|December 4, 2024
PubMed

Insights

Endoplasmic reticulum (ER) tubules hitchhike on Rab6-marked post-Golgi vesicles, a newly identified mechanism for ER movement. This vesicle-driven transport is crucial for ER positioning and organelle interaction within cells.

Area of Science:

  • Cell Biology
  • Molecular Motors
  • Organelle Dynamics

Background:

  • Peripheral endoplasmic reticulum (ER) tubules interact with organelles via membrane contact sites.
  • ER movement traditionally involves motor proteins or tip attachment complexes (TAC) along microtubules.
  • A third mechanism, hitchhiking, where vesicles pull ER tubules, was recently discovered.

Purpose of the Study:

  • To investigate if other Rab-vesicles, besides endosomes, can mediate ER hitchhiking.
  • To identify specific Rab proteins involved in ER hitchhiking.
  • To determine the functional significance of Rab-vesicle-mediated ER movement.

Main Methods:

  • Screening of Rab proteins for cotransport with ER tubules in U2OS cells.
  • Depletion of Rab6 and assessment of its impact on ER movement.
  • Relocation of Rab6-vesicles to the cell periphery to observe ER accumulation.
  • Analysis of TGN46 and Rab1-marked vesicles in ER hitchhiking.

Main Results:

  • Endoplasmic reticulum (ER) tubules were found to hitchhike on post-Golgi vesicles marked by Rab6 (isoforms a and b).
  • Rab6-ER hitchhiking is independent of ER-endolysosome contacts and TAC-mediated ER movement.
  • Depletion of Rab6 or its vesicle motility significantly reduced overall ER movement, and peripheral ER accumulation was observed upon vesicle relocation.

Conclusions:

  • Rab6-marked post-Golgi vesicles are essential for a subset of endoplasmic reticulum (ER) movements through hitchhiking.
  • ER hitchhiking on Rab-vesicles represents a significant and previously underappreciated mode of ER transport.
  • ER to Golgi vesicles marked by Rab1 also contribute to ER movement via hitchhiking.

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