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© The Rockefeller University Press,
0021-9525/2000//579 $5.00
The Journal of Cell Biology, Volume 148, Number 3,
, 2000 579-590
Original Article |
Functional Cis-Heterodimers of N- and R-Cadherins
shapiro{at}anguilla.physbio.mssm.edu
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.
Key Words: cadherins cell adhesion heterophilic binding synaptic adhesion dimerization
© 2000 The Rockefeller University Press
Abbreviations used in this paper: DiI, 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine; DiO, 3,3-dioctadecyloxacarbocyanine perchlorate; EC1, first extracellular domain; GFP, green fluorescence protein; Trp-2, tryptophan 2.
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