A systematic review of Sec24 cargo interactome

Abstract

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.

Stage-Specific COPII-Mediated Cargo Selectivity in African Trypanosomes

“…For instance, while S. cerevisiae encodes one paralogue of Sec23 ( Sec23p ), there are two paralogues of Sec23 ( Sec23A and Sec23B ) in mammals ( 44 , 45 ). For the cargo-capturing subunit Sec24, there are three paralogues in yeast (Sec24p, Lst1p, and Iss1p) and four in mammalians (Sec24A-D) ( 27 ). Unlike in trypanosomes, not all COPII paralogues are required for viability in these systems.…”

“…Sar1-GTP then undergoes a conformational change, embeds into the ER membrane, and recruits Sec23/Sec24 heterodimers via specific interaction with Sec23. The Sar1-Sec23/Sec24 “prebudding complex” is responsible for the capture of transmembrane cargo via interactions with Sec24 ( 27 ). Subsequently, after cargo capture, Sec13/Sec31 heterotetramers are recruited to the prebudding complex resulting in the deformation and budding of discrete COPII vesicles ( 28 , 29 ).…”

Cargo selection in endoplasmic reticulum–to–Golgi transport and relevant diseases

“…Given the role of SEC24 in cargo recruitment, the expansion of COPII paralogs is thought to have been driven to accommodate a greater diversity of secretory cargoes in mammals. Current evidence suggests that SEC24 paralogs within the same subgroup (SEC24A/B versus SEC24C/D) may exhibit largely but not entirely overlapping function, with larger differences in cargo-sorting signal affinity between the two subgroups ( 85 – 88 ).…”

Critical Determinants in ER-Golgi Trafficking of Enzymes Involved in Glycosylation

“…The sorting signal in the cargo protein plays a dominant role in the direct or indirect interaction between cargo proteins and components in the coat. The Sec24 subunit in the COPII complex is involved in cargo sorting and directly binds with the cargo protein [ 70 , 71 , 72 ]. The diverse cargo binding sites in the Sec24 protein recognize different cargo sorting signal motifs in cargo proteins, and multiple isoforms of Sec24 are involved in diverse cargo sorting [ 71 , 72 , 73 ].…”

“…The Sec24 subunit in the COPII complex is involved in cargo sorting and directly binds with the cargo protein [ 70 , 71 , 72 ]. The diverse cargo binding sites in the Sec24 protein recognize different cargo sorting signal motifs in cargo proteins, and multiple isoforms of Sec24 are involved in diverse cargo sorting [ 71 , 72 , 73 ]. For example, the ER-exit signal DxE [ 74 , 75 ], LxxLE [ 75 , 76 ], YxxNPF [ 77 ], triple arginine (RRR) motif [ 78 ], and ΦXΦXΦ motif of bovine anion exchanger 1 (AE1) [ 79 ] are recognized by Sec24.…”