title: P120-catenin is a novel desmoglein 3 interacting partner: identification of the p120-catenin association site of desmoglein 3.
abstract: P120-catenin (p120ctn) is an armadillo-repeat protein that directly binds to the intracytoplasmic domains of classical cadherins. p120ctn binding promotes the stabilization of cadherin complexes on the plasma membrane and thus positively regulates the adhesive activity of cadherins. Using co-immunoprecipitation, we show here that p120ctn associates to desmogleins (Dsg) 1 and 3. To determine which region is involved in the association between Dsg3 and p120ctn, we constructed mutant Dsg3 proteins, in which various cytoplasmic subdomains were removed. The tailless Dsg3 constructs Delta IA:AA1-641Dsg3 and Delta 641-714Dsg3, which do not contain the intracellular anchor (IA) region, did not coprecipitate with p120cn, nor did they colocalize at the plasma membrane. Immunocytochemical analysis revealed that p120ctn does not localize to desmosomes, but colocalizes with Dsg3 at the cell surface. A biotinylation assay for Dsg3 showed that biotinylated Delta 641-714Dsg3 was turned over more rapidly than wild-type Dsg3. These results indicate that the membrane proximal region (corresponding to residues 641-714) in the IA region of Dsg3 is necessary for complex formation with p120ctn, and to maintain free Dsg3 at the cell surface before it is integrated into desmosomes. In summary, we show that p120ctn is a novel interactor of the Dsg proteins, and may play a role in desmosome remodeling.
authors.affiliation: Department of Dermatology, Gifu University School of Medicine, Gifu City 501-1194, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Kanno
authors.forename: Yasuka
authors.initials: Y
authors.lastname: Isa
authors.forename: Yumi
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Miki
authors.initials: M
authors.lastname: Nagai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ozawa
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Kitajima
mesh_terms: D000818:Animals; D001665:Binding Sites; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000032:analysis / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry; D051183:Desmoglein 1 / Q000032:analysis / Q000378:metabolism; D051184:Desmoglein 3 / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D015603:Keratinocytes / Q000737:chemistry; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000032:analysis / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D000095002:Delta Catenin
chemical_list: D051177:Catenins; D015815:Cell Adhesion Molecules; D051183:Desmoglein 1; D051184:Desmoglein 3; C495300:Dsg3 protein, mouse; D010750:Phosphoproteins; D000095002:Delta Catenin