期刊
JOURNAL OF CELL SCIENCE
卷 125, 期 3, 页码 673-684出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.091355
关键词
COPII; ER export; Epithelial organization
类别
资金
- MRC [G117/553]
- BBSRC [E019633]
- BBSRC [BB/E019633/1] Funding Source: UKRI
- MRC [G0801848, G117/554] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E019633/1] Funding Source: researchfish
- Engineering and Physical Sciences Research Council [EP/C509404/1] Funding Source: researchfish
- Medical Research Council [G117/554, G0801848] Funding Source: researchfish
Epithelial morphogenesis is directed by interactions with the underlying extracellular matrix. Secretion of collagen and other matrix components requires efficient coat complex II (COPII) vesicle formation at the endoplasmic reticulum. Here, we show that suppression of the outer layer COPII component, Sec 13, in zebrafish embryos results in a disorganized gut epithelium. In human intestinal epithelial cells (Caco-2), Sec13 depletion causes defective epithelial polarity and organization on permeable supports. Defects are seen in the ability of cells to adhere to the substrate, form a monolayer and form intercellular junctions. When embedded in a three-dimensional matrix, Sec13-depleted Caco-2 cells form cysts but, unlike controls, are defective in lumen expansion. Incorporation of primary fibroblasts within the three-dimensional culture substantially restores normal morphogenesis. We conclude that efficient COPII-dependent secretion, notably assembly of Sec13-Sec31, is required to drive epithelial morphogenesis in both two- and three-dimensional cultures in vitro, as well as in vivo. Our results provide insight into the role of COPII in epithelial morphogenesis and have implications for the interpretation of epithelial polarity and organization assays in cell culture.
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