A systematic review of Sec24 cargo interactome

Endoplasmic reticulum (ER)-to-Golgi trafficking is an essential and highly conserved cellular process. The coat protein complex-II (COPII) arm of the trafficking machinery incorporates a wide array of cargo proteins into vesicles through direct or indirect interactions with Sec24, the principal subunit of the COPII coat. Approximately one-third of all mammalian proteins rely on the COPII-mediated secretory pathway for membrane insertion or secretion. There are four mammalian Sec24 paralogs and three yeast Sec24 paralogs with emerging evidence of paralog-specific cargo interaction motifs. Furthermore, individual paralogs also differ in their affinity for a subset of sorting motifs present on cargo proteins. As with many aspects of protein trafficking, we lack a systematic and thorough understanding of the interaction of Sec24 with cargoes. This systematic review focuses on the current knowledge of cargo binding to both yeast and mammalian Sec24 paralogs and their ER export motifs. The analyses show that Sec24 paralog specificity of cargo (and cargo receptors) range from exclusive paralog dependence or preference to partial redundancy. We also discuss how the Sec24 secretion system is hijacked by viral (eg, VSV-G, Hepatitis B envelope protein) and bacterial (eg, the enteropathogenic Escherichia coli type III secretion system effector NleA/EspI) pathogens.

Automated summary

The trafficking of cargo from the endoplasmic reticulum (ER) to the Golgi apparatus is a crucial cellular process involving the coat protein complex-II (COPII) and Sec24. Approximately one-third of mammalian proteins require the COPII-mediated secretory pathway for membrane insertion or secretion. There are distinct cargo interaction motifs for different Sec24 paralogs, leading to varying levels of specificity in cargo binding. Additionally, the Sec24 secretion system can be exploited by pathogens like viruses and bacteria.