RT Journal Article
SR Electronic
T1 Epithelial polarization in 3D matrix requires DDR1 signaling to regulate actomyosin contractility
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800276
DO 10.26508/lsa.201800276
VO 2
IS 1
A1 Pia Pernille Søgaard
A1 Noriko Ito
A1 Nanami Sato
A1 Yasuyuki Fujita
A1 Karl Matter
A1 Yoshifumi Itoh
YR 2019
UL https://www.life-science-alliance.org/content/2/1/e201800276.abstract
AB 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.