Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish
- Authors
- Niu, X., Gao, C., Jan Lo, L., Luo, Y., Meng, C., Hong, J., Hong, W., and Peng, J.
- ID
- ZDB-PUB-120529-7
- Date
- 2012
- Source
- Developmental Biology 367(2): 197-207 (Journal)
- Registered Authors
- Gao, Chuan, Peng, Jinrong
- Keywords
- Sec13, COPII complex, digestive organs, liver development, zebrafish
- MeSH Terms
-
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism*
- Cell Cycle Checkpoints
- Mutation
- Unfolded Protein Response
- RNA Splicing/genetics
- Morpholinos/genetics
- Molecular Sequence Data
- Gene Expression Regulation, Developmental
- Amino Acid Sequence
- Microscopy, Electron, Transmission
- Endoplasmic Reticulum/metabolism
- Cell Differentiation
- Intestinal Mucosa/cytology
- Intestinal Mucosa/embryology
- Intestinal Mucosa/metabolism
- Zebrafish Proteins/antagonists & inhibitors
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- Hepatocytes/cytology
- Hepatocytes/metabolism
- Gene Knockdown Techniques
- Animals
- Digestive System/embryology*
- Digestive System/metabolism*
- COP-Coated Vesicles/genetics
- COP-Coated Vesicles/metabolism*
- Apoptosis
- Chondrocytes/cytology
- Chondrocytes/metabolism
- Base Sequence
- Organogenesis
- PubMed
- 22609279 Full text @ Dev. Biol.
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.