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bioRxiv · 10.1101/2025.09.18.677214

Nanoscopy of Organelle Handoff Portals Reveals Direct Coupling between ER Remodeling and Microtubule-Based Transport

Park, J.-S.·LEE, I.-B.·Moon, H.-M.·Jeon, H.·Lee, M.·Kim, C.·Hong, S.-C.·Cho, M.
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Abstract

How biosynthetic organelles leave the endoplasmic reticulum (ER) and engage with microtubule tracks remains a central question. Combining interferometric scattering with fluorescence nanoscopy, we tracked nanometer-scale handoff events in living cells. ER-derived organelles undergo biased diffusion along ER tubules toward nearby microtubules. ER three-way junctions function as nanoscopic hubs where cargo pauses, contacts multiple microtubules, and then launches onto a track for long-range travel. Remarkably, the ER maintains a membrane tether to the departing cargo, extending its tubules and forming new junctions, thereby coupling inter-network transfer with membrane morphogenesis. These observations reveal an integrated mechanism that links organelle biogenesis, directional trafficking, and continual ER- and cellular remodeling, underscoring the ERs active role in steering transport and repurposing its own output within the crowded intracellular environment.

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Park, J.-S., LEE, I.-B., Moon, H.-M., Jeon, H., Lee, M., Kim, C., Hong, S.-C., Cho, M.. 2025-09-21. Nanoscopy of Organelle Handoff Portals Reveals Direct Coupling between ER Remodeling and Microtubule-Based Transport. https://doi.org/10.1101/2025.09.18.677214

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