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Protein transport

The secretory pathway gets a molecular framework

Nature Reviews Molecular Cell Biology volume 26, page 907 (2025)Cite this article

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In the discussion, Schekman wrote that “by providing criteria for the authentic reconstruction of individual events in vitro, the sec mutants may aid in a biochemical dissection of the secretory pathway.” Indeed, such efforts were underway in the Schekman lab and in Jim Rothman’s lab just down the Bay at Stanford University. In 1984, Rothman’s group developed a cell-free assay using cultured mammalian cells to measure transport of the vesicular stomatitis virus G protein between Golgi compartments. Transport depended on isolated Golgi membranes, a crude cytosol and ATP. Fractionation of this cytosol in subsequent studies identified specific protein factors required for intra-Golgi transport termed NSF, α-SNAP and coatomer (COPI). As both groups molecularly characterized transport factors, near the end of the 1980s the approaches converged and sequencing efforts revealed that Sec18 and NSF, Sec17 and α-SNAP, and Sec21 and γ-COPI, were homologues, respectively. This convergence provided crucial validation of both groups’ findings, merging the use of yeast genetics and cell-free systems to molecularly define the eukaryotic secretory pathway. With authenticated cell-free assays and genetic tools now available, researchers set out to reconstitute and dissect specific sub-reactions in the secretory pathway. It was a watershed moment for the trafficking community and illustrative of how genetic and biochemical approaches can be powerfully combined to define complex cellular processes.

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References

Original articles

  • Novick, P., Field, C. & Schekman, R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway. Cell 21, 205–215 (1980)

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  • Balch, W. E., Dunphy, W. G., Braell, W. A. & Rothman, J. E. Reconstitution of the transport of protein between successive compartments of the Golgi measured by the coupled incorporation of N-acetylglucosamine. Cell 39, 405–416 (1984)

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Biochemistry and Cell Biology, Geisel School of Medicine at Dartmouth, Hanover, NH, USA

    Charles Barlowe

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  1. Charles Barlowe
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Correspondence to Charles Barlowe.

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Barlowe, C. The secretory pathway gets a molecular framework. Nat Rev Mol Cell Biol 26, 907 (2025). https://doi.org/10.1038/s41580-025-00912-6

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