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Molecular organization of the eukaryotic secretory pathway

Mycroft-West, C. J.; Yee, N. B.- y.; Leanca, M. A.; Darrow, M. C.; Wu, L.

2026-07-29 cell biology
10.64898/2026.07.28.741320 bioRxiv
Show abstract

The eukaryotic secretory pathway is an essential subcellular network comprised of the endoplasmic reticulum (ER) and Golgi organelles. It mediates the trafficking of protein, lipid and other biomolecular cargoes throughout the cell, and is also the site of enzymatic modifications such as glycosylation that are vital for biological function. Complex interactions between resident functional proteins and cargo biomolecules drive myriad activities within the secretory pathway, but how these components organize within native milieu is still poorly understood. Here, we used cryo-electron tomography to survey the HeLa secretory pathway, revealing detailed features of its organellar structure. By quantitatively mapping protein distributions, we find that interactions within the HeLa secretory pathway are dominated by small dimeric complexes, stochastically distributed across both ER and Golgi membranes. Our survey of secretory pathway biomolecules provides new insights into putative trafficking and modification mechanisms, and highlights links between molecular organization and function within intracellular compartments.

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