title: Phosphorylation potential ofDrosophilaE-Cadherin intracellular domain is essential for development and adherens junction biosynthetic dynamics regulation.
abstract: Phosphorylation of a highly conserved serine cluster in the intracellular domain of E-Cadherin is essential for binding to β-Cateninin vitroIn cultured cells, phosphorylation of specific serine residues within the cluster is also required for regulation of adherens junction (AJ) stability and dynamics. However, much less is known about how such phosphorylation of E-Cadherin regulates AJ formation and dynamicsin vivoIn this report, we generated an extensive array ofDrosophilaE-Cadherin (DE-Cad) endogenous knock-in alleles that carry mutations targeting this highly conserved serine cluster. Analyses of these mutations suggest that the overall phosphorylation potential, rather than the potential site-specific phosphorylation, of the serine cluster enhances the recruitment of β-Catenin by DE-Cadin vivoMoreover, phosphorylation potential of the serine cluster only moderately increases the level of β-Catenin in AJs and is in fact dispensable for AJ formationin vivoNonetheless, phosphorylation-dependent recruitment of β-Catenin is essential for development, probably by enhancing the interactions between DE-Cad and α-Catenin. In addition, several phospho-mutations dramatically reduced the biosynthetic turnover rate of DE-Cad during apical-basal polarization, and such biosynthetically stable DE-Cad mutants specifically rescued the polarity defects in embryonic epithelia lacking the polarity proteins Stardust and Crumbs.
authors.affiliation: Department of Cell Biology, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA.
authors.forename: Yi-Jiun
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Department of Cell Biology, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA.|Department of Biotechnology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing 211166, People's Republic of China.
authors.forename: Juan
authors.identifier: 0000-0002-6259-4196
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Cell Biology, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA.
authors.forename: Lynn
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Cell Biology, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA.
authors.forename: Erin
authors.identifier: 0000-0001-9379-3457
authors.initials: E
authors.lastname: Austin
authors.affiliation: Department of Cell Biology, University of Pittsburgh Medical School, Pittsburgh, PA 15261, USA yhong@pitt.edu.
authors.forename: Yang
authors.identifier: 0000-0003-2252-0798
authors.initials: Y
authors.lastname: Hong
mesh_terms: D022005:Adherens Junctions / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D053898:Biosynthetic Pathways; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism*; D016764:Cell Polarity; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000737:chemistry* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D010766:Phosphorylation; D000072417:Protein Domains; D055550:Protein Stability; D012694:Serine / Q000378:metabolism; D013329:Structure-Activity Relationship; D051178:alpha Catenin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D050505:Mutant Proteins; D051178:alpha Catenin; D051176:beta Catenin; C501889:shg protein, Drosophila; D012694:Serine
keywords: Adherens junctions; Apical-basal polarity; Armadillo; Crb; DE-Cadherin; Drosophila; Sdt; Shotgun; α-Catenin; β-Catenin