title: Divergence of structural strategies for homophilic E-cadherin binding among bilaterians.
abstract: Homophilic binding of E-cadherins through their ectodomains is fundamental to epithelial cell-cell adhesion. Despite this, E-cadherin ectodomains have evolved differently in the vertebrate and insect lineages. Of the five rod-like, tandemly aligned extracellular cadherin domains of vertebrate E-cadherin, the tip extracellular cadherin domain plays a pivotal role in binding interactions. Comparatively, the six consecutive N-terminal extracellular cadherin domains of Drosophila E-cadherin, DE-cadherin (also known as Shotgun), can mediate adhesion; however, the underlying mechanism is unknown. Here, we report atomic force microscopy imaging of DE-cadherin extracellular cadherin domains. We identified a tightly folded globular structure formed by the four N-terminal-most extracellular cadherin domains stabilized by the subsequent two extracellular cadherin domains. Analysis of hybrid cadherins from different insects indicated that the E-cadherin globular portion is associated with determining homophilic binding specificity. The second to fourth extracellular cadherin domains were identified as the minimal portion capable of mediating exclusive homophilic binding specificity. Our findings suggest that the N-terminal-most four extracellular cadherin domains of insect E-cadherin are functionally comparable with the N-terminal-most single extracellular cadherin domain of vertebrate E-cadherin, but that their mechanisms might significantly differ. This work illuminates the divergence of structural strategies for E-cadherin homophilic binding among bilaterians.
authors.affiliation: JT Biohistory Research Hall, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, Japan R&D Group, Olympus Corporation, 2-3 Kuboyama-cho, Hachioji-shi, Tokyo 192-8512, Japan.
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Nishiguchi
authors.affiliation: R&D Group, Olympus Corporation, 2-3 Kuboyama-cho, Hachioji-shi, Tokyo 192-8512, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yagi
authors.affiliation: R&D Group, Olympus Corporation, 2-3 Kuboyama-cho, Hachioji-shi, Tokyo 192-8512, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Sakai
authors.affiliation: JT Biohistory Research Hall, 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan Department of Biological Sciences, Graduate School of Science, Osaka University, Osaka, Japan hoda@brh.co.jp.
authors.forename: Hiroki
authors.identifier: 0000-0003-4424-988X
authors.initials: H
authors.lastname: Oda
mesh_terms: D000818:Animals; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism*; D017124:Conserved Sequence; D005110:Extracellular Space / Q000378:metabolism; D007313:Insecta / Q000378:metabolism; D007448:Invertebrates / Q000378:metabolism*; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D000072417:Protein Domains; D014714:Vertebrates / Q000378:metabolism
chemical_list: D015820:Cadherins
keywords: Adherens junction; Atomic force microscopy; Cadherin; Cell adhesion; Evolution; Insect