Casein kinase 1 is a novel negative regulator of E-cadherin-based cell-cell contacts.
Cadherins are the most crucial membrane proteins for the formation of tight and compact cell-cell contacts. Cadherin-based cell-cell adhesions are dynamically established and/or disrupted during various physiological and pathological processes. However, the molecular mechanisms that regulate cell-cell contacts are not fully understood. In this paper, we report a novel functional role of casein kinase 1 (CK1) in the regulation of cell-cell contacts. Firstly, we observed that IC261, a specific inhibitor of CK1, stabilizes cadherin-based cell-cell contacts, whereas the overexpression of CK1 disrupts them. CK1 colocalizes with E-cadherin and phosphorylates the cytoplasmic domain of E-cadherin in vitro and in a cell culture system. We show that the major CK1 phosphorylation site of E-cadherin is serine 846, a highly conserved residue between classical cadherins. Constitutively phosphorylated E-cadherin (S846D) is unable to localize at cell-cell contacts and has decreased adhesive activity. Furthermore, phosphorylated E-cadherin (S846D) has weaker interactions with beta-catenin and is internalized more efficiently than wild-type E-cadherin. These data indicate that CK1 is a novel negative regulator of cadherin-based cell-cell contacts.
Dupre-Crochet
Sophie
S
MRC Laboratory for Molecular Cell Biology and Cell Biology Unit, and Department of Biology, University College London, Gower Street, London, United Kingdom.
Figueroa
Angélica
A
Hogan
Catherine
C
Ferber
Emma C
EC
Bialucha
Carl Uli
CU
Adams
Joanna
J
Richardson
Emily C N
EC
Fujita
Yasuyuki
Y
D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D047389:Casein Kinase I / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004705:Endocytosis / Q000502:physiology; D006801:Humans; D007211:Indoles / Q000378:metabolism; D007365:Intercellular Junctions / Q000378:metabolism*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D010696:Phloroglucinol / Q000031:analogs & derivatives / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D016415:Sequence Alignment; D012694:Serine / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; C411652:IC 261; D007211:Indoles; D007527:Isoenzymes; D051176:beta Catenin; D012694:Serine; D010696:Phloroglucinol; D047389:Casein Kinase I