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bioRxiv · 10.1101/2025.02.12.638000

Dynamic regulation of Sec24C by phosphorylation and O-GlcNAcylation during cell cycle progression

Georgiou, G. R.·Hirata, T.·Soderblom, E. J.·Homoelle, R.·Maiwald, J.·Boyce, M.
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Abstract

During mitosis, eukaryotic cells cease anterograde trafficking from the endoplasmic reticulum (ER) towards the Golgi. This cessation corresponds with the dispersal of the COPII transport protein, Sec24C, from juxtanuclear ER exit sites (ERES) into a diffusely cytosolic pool. Redistribution of Sec24 paralogs and other core COPII proteins may underlie the mitotic pause in secretion and may be required for the equal inheritance of endomembrane organelles and machinery by both daughter cells. Therefore, it is important to understand the mechanisms governing the mitotic relocalization of COPII components. Here, we explore the role of post-translational modifications (PTMs) of the model COPII protein Sec24C in this phenotypic switch during mitosis. In interphase, Sec24C is modified by O-linked {beta}-N-acetylglucosamine (O-GlcNAc), and we show that this glycan is rapidly removed upon mitotic entry, influencing the timing of Sec24C dispersal. Additionally, we identify novel, cell cycle phase-enriched phosphorylation events on Sec24C, including phosphosites that regulate the stability and localization of the protein, providing the first systematic characterization of dynamic PTMs on any Sec24 protein. Together, our data support the hypothesis that phosphorylation and glycosylation of Sec24C act in concert to induce rapid dispersal upon mitotic entry and may promote equal partitioning of the endomembrane system to daughter cells after division.

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Georgiou, G. R., Hirata, T., Soderblom, E. J., Homoelle, R., Maiwald, J., Boyce, M.. 2025-02-14. Dynamic regulation of Sec24C by phosphorylation and O-GlcNAcylation during cell cycle progression. https://doi.org/10.1101/2025.02.12.638000

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