Functional cis-Heterodimers of N- and R-Cadherins

doi:10.1083/jcb.148.3.579

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© The Rockefeller University Press, 0021-9525/2000/2/579/ $5.00
The Journal of Cell Biology, Volume 148, Number 3, February 7, 2000 579-590

Original Article

Functional cis-Heterodimers of N- and R-Cadherins

Wei-Song Shan^a, Hidekazu Tanaka^a, Greg R. Phillips^a, Kirsten Arndt^a, Mika Yoshida^a, David R. Colman^a, and Lawrence Shapiro^b
^a Department of Biochemistry and Molecular Biology, Programs in Cell Adhesion and Structural Biology
^b Department of Physiology and Biophysics, The Mount Sinai School of Medicine of New York University, New York, New York 10029

Correspondence to: Lawrence Shapiro, Structural Biology Program, Department of Physiology and Biophysics, The Mount Sinai School of Medicine, 1425 Madison Avenue, NY, NY 10029. Tel:(212) 659-8651 Fax:(212) 849-2456 E-mail:shapiro{at}anguilla.physbio.mssm.edu.

Classical cadherins form parallel cis-dimers that emanate froma single cell surface. It is thought that the cis-dimeric formis active in cell–cell adhesion, whereas cadherin monomersare likely to be inactive. Currently, cis-dimers have been shownto exist only between cadherins of the same type. Here, we showthe specific formation of cis-heterodimers between N- and R-cadherins.E-cadherin cannot participate in these complexes. Cells coexpressingN- and R-cadherins show homophilic adhesion in which these proteinscoassociate at cell–cell interfaces. We performed site-directed mutagenesis studies, the results of which support thestrand dimer model for cis-dimerization. Furthermore, we showthat when N- and R-cadherins are coexpressed in neurons in vitro,the two cadherins colocalize at certain neural synapses, implyingbiological relevance for these complexes. The present studyprovides a novel paradigm for cadherin interaction whereby selectivecis-heterodimer formation may generate new functional unitsto mediate cell–cell adhesion.

Key Words: cadherins, cell adhesion, heterophilic binding, synaptic adhesion,dimerization

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