title: Sec13 safeguards the integrity of the endoplasmic reticulum and organogenesis of the digestive system in zebrafish.
abstract: 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 sec13(sq198) 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 sec13(sq198), 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.
authors.affiliation: Key Laboratory for Molecular Animal Nutrition, Ministry of Education, College of Animal Sciences, Zhejiang University, Hangzhou, PR China.
authors.forename: Xubo
authors.initials: X
authors.lastname: Niu
authors.forename: Chuan
authors.initials: C
authors.lastname: Gao
authors.forename: Li
authors.initials: L
authors.lastname: Jan Lo
authors.forename: Yue
authors.initials: Y
authors.lastname: Luo
authors.forename: Chunmei
authors.initials: C
authors.lastname: Meng
authors.forename: Jian
authors.initials: J
authors.lastname: Hong
authors.forename: Wanjin
authors.initials: W
authors.lastname: Hong
authors.forename: Jinrong
authors.initials: J
authors.lastname: Peng
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001483:Base Sequence; D022181:COP-Coated Vesicles / Q000235:genetics / Q000378:metabolism*; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D004064:Digestive System / Q000196:embryology* / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D009154:Mutation; D038081:Organogenesis; D012326:RNA Splicing / Q000235:genetics; D056811:Unfolded Protein Response; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D060172:Morpholinos; D029961:Zebrafish Proteins