ZO-1 interactions with F-actin and occludin direct epithelial polarization and single lumen specification in 3D culture
| Autor: | Mary M. Buschmann, Yitang Wang, Aaron Buckley, Matthew A. Odenwald, Jeffrey D. Hildebrand, Nora E. Joseph, Alan S. Fanning, Roman Pavlyuk, Nitesh Shashikanth, Wangsun Choi, Jerrold R. Turner, Michael H. Warren, Ben Margolis |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Scaffold protein Alpha catenin Cell Culture Techniques Mitosis Biology Occludin Cell Line Tight Junctions 03 medical and health sciences Cell polarity Morphogenesis Humans Actin Cell Proliferation Tight junction Cell Polarity Epithelial Cells Cell Biology Actins Transport protein Cell biology Protein Transport 030104 developmental biology Phenotype Gene Knockdown Techniques Zonula Occludens-1 Protein alpha Catenin Lumen (unit) Protein Binding Research Article |
| Zdroj: | Journal of cell science. 130(1) |
| ISSN: | 1477-9137 |
| Popis: | Epithelia within tubular organs form and expand lumens. Failure of these processes can result in serious developmental anomalies. Although tight junction assembly is crucial to epithelial polarization, the contribution of specific tight junction proteins to lumenogenesis is undefined. Here, we show that ZO-1 (also known as TJP1) is necessary for the formation of single lumens. Epithelia lacking this tight junction scaffolding protein form cysts with multiple lumens and are defective in the earliest phases of polarization, both in two and three dimensions. Expression of ZO-1 domain-deletion mutants demonstrated that the actin-binding region and U5-GuK domain are crucial to single lumen development. For actin-binding region, but not U5-GuK domain, mutants, this could be overcome by strong polarization cues from the extracellular matrix. Analysis of the U5-GuK binding partners shroom2, α-catenin and occludin showed that only occludin deletion led to multi-lumen cysts. Like ZO-1-deficiency, occludin deletion led to mitotic spindle orientation defects. Single lumen formation required the occludin OCEL domain, which binds to ZO-1. We conclude that ZO-1-occludin interactions regulate multiple phases of epithelial polarization by providing cell-intrinsic signals that are required for single lumen formation. |
| Databáze: | OpenAIRE |
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