Claudins and JAM-A coordinately regulate tight junction formation and epithelial polarity
| Autor: | Tetsuhisa Otani, Takashi Miura, Taichi Sugawara, Mikio Furuse, Thanh Phuong Nguyen, Kyoko Furuse, Shinsaku Tokuda, Kei Sugihara, Klaus Ebnet |
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| Rok vydání: | 2019 |
| Předmět: |
Polarity (physics)
education Biology Article Madin Darby Canine Kidney Cells Tight Junctions 03 medical and health sciences Dogs 0302 clinical medicine Cell polarity medicine Animals Claudin Research Articles Cells Cultured 030304 developmental biology Epithelial polarity 0303 health sciences Tight junction Cell Polarity Epithelial Cells Cell Biology humanities Epithelium Cell biology Junctional Adhesion Molecule A medicine.anatomical_structure Membrane protein Cytoplasm Claudins 030217 neurology & neurosurgery |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Tight junctions (TJs) are a key component of barriers formed by polarized epithelial cells. Otani et al. found that the scaffolding proteins ZO-1/ZO-2 are essential for TJ formation and epithelial polarity. Claudins regulate the TJ strand and electrolyte permeability barrier, while JAM-A regulates membrane apposition and the macromolecule permeability barrier. Claudins and JAM-A act redundantly in regulating epithelial polarity. Tight junctions (TJs) establish the epithelial barrier and are thought to form a membrane fence to regulate epithelial polarity, although the roles of TJs in epithelial polarity remain controversial. Claudins constitute TJ strands in conjunction with the cytoplasmic scaffolds ZO-1 and ZO-2 and play pivotal roles in epithelial barrier formation. However, how claudins and other TJ membrane proteins cooperate to organize TJs remains unclear. Here, we systematically knocked out TJ components by genome editing and show that while ZO-1/ZO-2–deficient cells lacked TJ structures and epithelial barriers, claudin-deficient cells lacked TJ strands and an electrolyte permeability barrier but formed membrane appositions and a macromolecule permeability barrier. Moreover, epithelial polarity was disorganized in ZO-1/ZO-2–deficient cells, but not in claudin-deficient cells. Simultaneous deletion of claudins and a TJ membrane protein JAM-A resulted in a loss of membrane appositions and a macromolecule permeability barrier and in sporadic epithelial polarity defects. These results demonstrate that claudins and JAM-A coordinately regulate TJ formation and epithelial polarity. |
| Databáze: | OpenAIRE |
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