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bioRxiv · 10.1101/2025.06.26.661719

The mechanistic basis of cargo selection during Golgi maturation

Taylor, R. J.·Zubkov, N.·Ciazynska, K. A.·Kaufman, J. G.·Tagiltsev, G.·Owen, D. J.·Briggs, J.·Munro, S.
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Abstract

The multiple cisternae of the Golgi apparatus contain resident membrane proteins crucial for lipid and protein glycosylation. How Golgi residents remain in their designated compartments despite a constant flow of secretory cargo is incompletely understood. Here, we determined the structure of the COPI vesicle coat containing GOLPH3, an adaptor protein that binds the cytosolic tails of many Golgi residents. The structure, together with structure-guided mutagenesis and functional assays, reveals how GOLPH3 uses coincidence detection of COPI and lipid to engage Golgi residents preferentially at late cisternae. Our findings rationalize the logic of cisternal maturation and explain how COPI can engage different types of substrates in different Golgi cisternae to retrieve some proteins back to the ER while retaining others within the Golgi apparatus.

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Taylor, R. J., Zubkov, N., Ciazynska, K. A., Kaufman, J. G., Tagiltsev, G., Owen, D. J., Briggs, J., Munro, S.. 2025-06-26. The mechanistic basis of cargo selection during Golgi maturation. https://doi.org/10.1101/2025.06.26.661719

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