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Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility

Søgaard, Pia Pernille; Ito, Noriko; Sato, Nanami; Fujita, Yasuyuki; Matter, Karl; Itoh, Yoshifumi; (2019) Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility. Life Science Alliance , 2 (1) , Article e201800276. 10.26508/lsa.201800276. Green open access

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Abstract

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.

Type: Article
Title: Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility
Open access status: An open access version is available from UCL Discovery
DOI: 10.26508/lsa.201800276
Publisher version: https://doi.org/10.26508/lsa.201800276
Language: English
Additional information: © 2019 Søgaard et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Keywords: actomyosin; DDR1; collagen; epithelial polarity; MT1-MMP; ROCK
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/10067853
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