Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish

The Sec13-Sec31 heterotetramer serves as the outer coat in the COPII complex, which mediates protein trafficking from the endoplasmic reticulum (ER) to the Golgi apparatus. Although it has been studied in depth in yeast and cultured cells, the role of COPII in organogenesis in a multicellular organism has not. We report here that a zebrafish sec13sq198 mutant, which exhibits a phenotype of hypoplastic digestive organs, has a mutation in the sec13 gene. The mutant gene encodes a carboxyl-terminus-truncated Sec13 that loses its affinity to Sec31a, which leads to disintegration of the ER structure in various differentiated cells in sec13sq198, including chondrocytes, intestinal epithelial cells and hepatocytes. Disruption of the ER structure activates an unfolded protein response that eventually causes the cells to undergo cell-cycle arrest and cell apoptosis, which arrest the growth of developing digestive organs in the mutant. Our data provide the first direct genetic evidence that COPII function is essential for the organogenesis of the digestive system.

► sec13sq198 mutation disrupts the organogenesis of digestive organs. ► sec13sq198 mutation disrupts the integrity of the ER. ► sec13sq198 mutation leads to activation of the unfolded protein response (UPR). ► sec13sq198 mutation causes cell cycle arrest in the digestive organs. ► sec13sq198 mutation induces cell apoptosis in the digestive organs.