title: A complex of Protocadherin-19 and N-cadherin mediates a novel mechanism of cell adhesion.
abstract: During embryonic morphogenesis, adhesion molecules are required for selective cell-cell interactions. The classical cadherins mediate homophilic calcium-dependent cell adhesion and are founding members of the large and diverse cadherin superfamily. The protocadherins are the largest subgroup within this superfamily, yet their participation in calcium-dependent cell adhesion is uncertain. In this paper, we demonstrate a novel mechanism of adhesion, mediated by a complex of Protocadherin-19 (Pcdh19) and N-cadherin (Ncad). Although Pcdh19 alone is only weakly adhesive, the Pcdh19-Ncad complex exhibited robust adhesion in bead aggregation assays, and Pcdh19 appeared to play the dominant role. Adhesion by the Pcdh19-Ncad complex was unaffected by mutations that disrupt Ncad homophilic binding but was inhibited by a mutation in Pcdh19. In addition, the complex exhibited homophilic specificity, as beads coated with Pcdh19-Ncad did not intermix with Ncad- or Pcdh17-Ncad-coated beads. We propose a model in which association of a protocadherin with Ncad acts as a switch, converting between distinct binding specificities.
authors.affiliation: Department of Neuroscience, School of Biomedical Science, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Michelle R
authors.initials: MR
authors.lastname: Emond
authors.forename: Sayantanee
authors.initials: S
authors.lastname: Biswas
authors.forename: Cheasequah J
authors.initials: CJ
authors.lastname: Blevins
authors.forename: James D
authors.initials: JD
authors.lastname: Jontes
mesh_terms: D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002449:Cell Aggregation; D006224:Cricetinae; D057809:HEK293 Cells; D006801:Humans; D046912:Multiprotein Complexes; D000091363:Protocadherins; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*
chemical_list: D015820:Cadherins; D046912:Multiprotein Complexes; C513786:N-cadherin, zebrafish; C545892:Pcdh19 protein, zebrafish; D000091363:Protocadherins; D029961:Zebrafish Proteins