A systematic review of Sec24 cargo interactome

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Endoplasmic reticulum (ER)-to-Golgi trafficking is crucial for cellular function, involving the coat protein complex-II (COPII) machinery.
• Sec24, a key subunit of COPII, mediates cargo protein incorporation into vesicles.
• Approximately one-third of mammalian proteins utilize the COPII pathway for secretion or membrane insertion.

Purpose of the Study:

• To systematically review current knowledge on cargo binding interactions with yeast and mammalian Sec24 paralogs.
• To elucidate the specificity of cargo recognition motifs and their interaction with different Sec24 paralogs.
• To explore how pathogens exploit the Sec24-mediated secretion system.

Main Methods:

• Systematic literature review of studies on Sec24-cargo interactions.
• Analysis of cargo binding specificity across different Sec24 paralogs in yeast and mammals.
• Review of documented instances of pathogen manipulation of the Sec24 secretion pathway.

Main Results:

• Sec24 paralogs exhibit varying degrees of specificity in cargo binding, ranging from exclusive dependence to partial redundancy.
• Evidence suggests distinct cargo interaction motifs are recognized by different Sec24 paralogs.
• Pathogens like viruses (VSV-G, Hepatitis B) and bacteria (E. coli NleA/EspI) have evolved mechanisms to hijack the Sec24 secretion system.

Conclusions:

• Understanding Sec24 paralog specificity is key to comprehending ER-to-Golgi protein trafficking.
• Sec24-cargo interactions are diverse and critical for normal cellular processes.
• Pathogen strategies highlight the importance and vulnerability of the Sec24-mediated secretory pathway.