Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum
Procollagen requires COPII coat proteins for export from the endoplasmic reticulum (ER). SEC24 is the major component of the COPII proteins that selects cargo during COPII vesicle assembly. There are four paralogs (A to D) of SEC24 in mammals, which are classified into two subgroups. Pathological mutations in SEC24D cause osteogenesis imperfecta with craniofacial dysplasia in humans and sec24d mutant fish also recapitulate this phenotypes. Consistent with the skeletal phenotypes, the secretion of collagen was severely defective in mutant fish, emphasizing the importance of SEC24D in collagen secretion. However, SEC24D patient derived fibroblasts show only a mild secretion phenotype, suggesting tissue-specificity in the secretion process. To explore this possibility, we generated Sec24d knockout (KO) mice. Homozygous KO mice died prior to bone development. When we analyzed embryonic and extraembryonic tissues of mutant animals, we observed tissue-dependent defects of procollagen processing and ER export. The spacial patterns of these defects mirrored with SEC24B deficiency. By systematically knocking down the expression of Sec24 paralogs, we determined that, in addition to SEC24C and SEC24D, SEC24A and SEC24B also contribute to collagen secretion. In contrast, fibronectin 1 preferred either SEC24C or SEC24D. On the basis of our results, we propose that procollagen interacts with multiple SEC24 paralogs for efficient export from the ER, and that this is the basis for tissue-specific phenotypes resulting from SEC24 paralog deficiency.
This is a pre-print of the article Lu, Chung-Ling, Jacob Cain, Jon Brudvig, Steven Ortmeier, Simeon Boyadjiev, Jill M. Weimer, and Jinoh Kim. "Collagen has a unique SEC24 preference for efficient export from the endoplasmic reticulum." bioRxiv (2021). DOI: 10.1101/2021.02.23.431880. Posted with permission.