Gallegos, Lisa LeonNg, Mei RosaSowa, Mathew E.Selfors, LauraWhite, AnneZervantonakis, IoannisSingh, PragyaDhakal, SabinHarper, J. WadeBrugge, Joan2016-07-142016Gallegos, Lisa Leon, Mei Rosa Ng, Mathew E. Sowa, Laura M. Selfors, Anne White, Ioannis K. Zervantonakis, Pragya Singh, Sabin Dhakal, J. Wade Harper, and Joan S. Brugge. 2016. “A protein interaction map for cell-cell adhesion regulators identifies DUSP23 as a novel phosphatase for β-catenin.” Scientific Reports 6 (1): 27114. doi:10.1038/srep27114. http://dx.doi.org/10.1038/srep27114.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:27662210Cell-cell adhesion is central to morphogenesis and maintenance of epithelial cell state. We previously identified 27 candidate cell-cell adhesion regulatory proteins (CCARPs) whose down-regulation disrupts epithelial cell-cell adhesion during collective migration. Using a protein interaction mapping strategy, we found that 18 CCARPs link to core components of adherens junctions or desmosomes. We further mapped linkages between the CCARPs and other known cell-cell adhesion proteins, including hits from recent screens uncovering novel components of E-cadherin adhesions. Mechanistic studies of one novel CCARP which links to multiple cell-cell adhesion proteins, the phosphatase DUSP23, revealed that it promotes dephosphorylation of β-catenin at Tyr 142 and enhances the interaction between α- and β-catenin. DUSP23 knockdown specifically diminished adhesion to E-cadherin without altering adhesion to fibronectin matrix proteins. Furthermore, DUSP23 knockdown produced “zipper-like” cell-cell adhesions, caused defects in transmission of polarization cues, and reduced coordination during collective migration. Thus, this study identifies multiple novel connections between proteins that regulate cell-cell interactions and provides evidence for a previously unrecognized role for DUSP23 in regulating E-cadherin adherens junctions through promoting the dephosphorylation of β-catenin.en-USJournal Article2016-07-1410.1038/srep27114