Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility
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- Pia Pernille Søgaard
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
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- Noriko Ito
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
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- Nanami Sato
- Institute for Genetic Medicine, Division of Molecular Oncology, Hokkaido University, Sapporo, Japan
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- Yasuyuki Fujita
- Institute for Genetic Medicine, Division of Molecular Oncology, Hokkaido University, Sapporo, Japan
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- Karl Matter
- UCL Institute of Ophthalmology, University College London, London, UK
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- Yoshifumi Itoh
- Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK
書誌事項
- 公開日
- 2019-02
- 資源種別
- journal article
- 権利情報
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- https://creativecommons.org/licenses/by/4.0/
- DOI
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- 10.26508/lsa.201800276
- 公開者
- Life Science Alliance, LLC
説明
<jats:p>Epithelial cells form sheets and tubules in various epithelial organs and establish apicobasal polarity and asymmetric vesicle transport to provide functionality in these structures. However, the molecular mechanisms that allow epithelial cells to establish polarity are not clearly understood. Here, we present evidence that the kinase activity of the receptor tyrosine kinase for collagen, discoidin domain receptor 1 (DDR1), is required for efficient establishment of epithelial polarity, proper asymmetric protein secretion, and execution of morphogenic programs. Lack of DDR1 protein or inhibition of DDR1 kinase activity disturbed tubulogenesis, cystogenesis, and the establishment of epithelial polarity and caused defects in the polarized localization of membrane-type 1 matrix metalloproteinase (MT1-MMP), GP135, primary cilia, laminin, and the Golgi apparatus. Disturbed epithelial polarity and cystogenesis upon DDR1 inhibition was caused by excess ROCK (rho-associated, coiled-coil-containing protein kinase)-driven actomyosin contractility, and pharmacological inhibition of ROCK was sufficient to correct these defects. Our data indicate that a DDR1-ROCK signaling axis is essential for the efficient establishment of epithelial polarity.</jats:p>
収録刊行物
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- Life Science Alliance
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Life Science Alliance 2 (1), e201800276-, 2019-02
Life Science Alliance, LLC
- Tweet
キーワード
- collagen
- Male
- 571
- Golgi Apparatus
- Madin Darby Canine Kidney Cells
- Mice
- Dogs
- Discoidin Domain Receptor 1
- Contactin 1
- MT1-MMP
- ROCK
- Matrix Metalloproteinase 14
- Animals
- Humans
- DDR1
- Cilia
- epithelial polarity
- Research Articles
- rho-Associated Kinases
- actomyosin
- Cell Polarity
- Epithelial Cells
- Actomyosin
- Mice, Inbred C57BL
- Organoids
- Female
- Laminin
- Caco-2 Cells
詳細情報 詳細情報について
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- CRID
- 1362539018713428736
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- ISSN
- 25751077
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- PubMed
- 30760555
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE
