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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.

Original publication

DOI

10.26508/lsa.201800276

Type

Journal article

Journal

Life sci alliance

Publication Date

02/2019

Volume

2

Keywords

Actomyosin, Animals, Caco-2 Cells, Cell Polarity, Cilia, Contactin 1, Discoidin Domain Receptor 1, Dogs, Epithelial Cells, Female, Golgi Apparatus, Humans, Laminin, Madin Darby Canine Kidney Cells, Male, Matrix Metalloproteinase 14, Mice, Mice, Inbred C57BL, Organoids, rho-Associated Kinases