title: Functional cis-heterodimers of N- and R-cadherins.
abstract: Classical cadherins form parallel cis-dimers that emanate from a single cell surface. It is thought that the cis-dimeric form is active in cell-cell adhesion, whereas cadherin monomers are likely to be inactive. Currently, cis-dimers have been shown to exist only between cadherins of the same type. Here, we show the specific formation of cis-heterodimers between N- and R-cadherins. E-cadherin cannot participate in these complexes. Cells coexpressing N- and R-cadherins show homophilic adhesion in which these proteins coassociate at cell-cell interfaces. We performed site- directed mutagenesis studies, the results of which support the strand dimer model for cis-dimerization. Furthermore, we show that when N- and R-cadherins are coexpressed in neurons in vitro, the two cadherins colocalize at certain neural synapses, implying biological relevance for these complexes. The present study provides a novel paradigm for cadherin interaction whereby selective cis-heterodimer formation may generate new functional units to mediate cell-cell adhesion.
authors.affiliation: Department of Biochemistry and Molecular Biology, Program in Cell Adhesion, The Mount Sinai School of Medicine, New York University, New York 10029, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Shan
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: G R
authors.initials: GR
authors.lastname: Phillips
authors.forename: K
authors.initials: K
authors.lastname: Arndt
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: D R
authors.initials: DR
authors.lastname: Colman
authors.forename: L
authors.initials: L
authors.lastname: Shapiro
mesh_terms: D000818:Animals; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D002450:Cell Communication; D019281:Dimerization; D015870:Gene Expression; D006168:Guinea Pigs; D007365:Intercellular Junctions; D007739:L Cells; D051379:Mice; D011817:Rabbits; D051381:Rats; D013569:Synapses; D014364:Tryptophan / Q000378:metabolism
chemical_list: D015820:Cadherins; C083970:R-cadherin; D014364:Tryptophan