title: In vivo ultrastructural localization of the desmoglein 3 adhesive interface to the desmosome mid-line.
abstract: Desmoglein (Dsg) is a cadherin cell-cell adhesion molecule located in desmosomes and its precise mechanism for cell-cell adhesion still remains to be elucidated. Opposing cadherin molecules may adhere to the N-terminal EC1 domains, or the entire length of the extracellular (EC) domains may overlap. To solve this controversy, we performed immunoelectron microscopy to map the Dsg3 epitopes in desmosomes. Three different hybridoma cell lines producing anti-Dsg3 monoclonal antibodies (mAb) were intraperitoneally injected into immunodeficient mice and the precise ultrastructural location of bound IgG between the mucosal epithelial cells in vivo was statistically measured and analyzed. The binding site of the AK23 mAb that recognizes the N-terminal EC1 domain was localized to the electron-dense mid-line of desmosomes. The binding sites of AK7 and AK18, which recognize the C-terminal membrane proximal and middle portions of the EC domains, were localized to the desmosomal region proximal to the membrane and the region between the plasma membrane and the dense mid-line, respectively. These results indicate that the N-terminal regions of Dsg3 from opposing cells interact at the dense mid-line of desmosomes where EC1 overlaps.
authors.affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Shimizu
authors.forename: Akira
authors.initials: A
authors.lastname: Ishiko
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ota
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Oka
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tsunoda
authors.forename: Masayuki
authors.initials: M
authors.lastname: Amagai
authors.forename: Takeji
authors.initials: T
authors.lastname: Nishikawa
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000276:immunology; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; D003896:Desmosomes / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D016253:Microscopy, Immunoelectron
chemical_list: D000911:Antibodies, Monoclonal; D003598:Cytoskeletal Proteins; D051184:Desmoglein 3; D051182:Desmogleins; D051180:Desmoplakins; C495300:Dsg3 protein, mouse