| Sec24C functions as one of four paralogs (A-D) in the Sec24 family, key cargo adaptor components of the COPII coat protein complex that mediate anterograde transport of secretory proteins from the endoplasmic reticulum to the Golgi apparatus. It features a conserved β-propeller and β-sandwich architecture that creates multiple cargo-binding pockets for selective recognition of transmembrane proteins and adaptors via di-acidic or di-hydrophobic motifs on their cytoplasmic tails. Sec24C assembles with Sec23 into the inner COPII coat upon Sar1 GTPase recruitment to ER exit sites, directly engaging client cargoes like CFTR, connexins, and procollagens to concentrate them into nascent vesicles while stimulating Sar1 GTP hydrolysis through Sec23's GAP activity; this pre-budding complex then recruits the outer Sec13/31 cage to drive membrane curvature, scission, and vesicle release, with Sec24C's distinct binding sites enabling paralog-specific sorting that avoids pathway saturation. Post-translational modifications like phosphorylation dynamically tune Sec24C's affinity for cargoes during stress, while its interaction with p24 adaptors facilitates clearance of misfolded proteins via ER-to-lysosome routes, bypassing Golgi trafficking. Sec24C sustains neuronal proteostasis and polarity by trafficking ion channels, receptors, and polarity determinants in post-mitotic neurons, positioning it as critical for studying ER stress responses where isoform redundancy (e.g., with Sec24D) reveals tissue-specific vulnerabilities; in hepatocytes, it drives lysosomal acidification to counter lipid accumulation, influencing metabolic flux. Its broad expression supports ubiquitous secretory demands, but high neuronal enrichment guides brain-specific models for trafficking defects. Dysregulation through deficiency triggers ER stress, UPR activation via PERK/ATF4/CHOP, and apoptotic neuronal loss, while mutations disrupt glycosylation and autophagy, linking to neurodevelopmental disorders. |
Lane 1: T-47D, Lane 2: A204, Lane 3: Hela, Lane 4: K562
