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Published online 14 January 2002. doi:10.1083/jcb.200108040
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© The Rockefeller University Press, 0021-9525/2002/1/389 $5.00
The Journal of Cell Biology, Volume 156, Number 2, January 21, 2002 389-400

Article

Cadherin-mediated cell sorting not determined by binding or adhesion specificity



Carien M. Niessen and Barry M. Gumbiner

Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021

Address correspondence to Barry M. Gumbiner, Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., Box 564, New York, NY 10021. Tel.: (212) 639-6146. Fax: (212) 717-3047. E-mail: b-gumbiner{at}ski.mskcc.org

Cadherin adhesion molecules play important roles in the establishment of tissue boundaries. Cells expressing different cadherins sort out from each other in cell aggregation assays. To determine the contribution of cadherin binding and adhesion specificity to the sorting process, we examined the adhesion of cells to different purified cadherin proteins. Chinese hamster ovary cell lines expressing one of four different cadherins were allowed to bind to the purified cadherin extracellular domains of either human E-cadherin or Xenopus C-cadherin, and the specificity of adhesion was compared with cell-sorting assays. None of the different cadherin-expressing cells exhibited any adhesive specificity toward either of the two purified cadherin substrates, even though these cadherins differ considerably in their primary sequence. In addition, all cells exhibited similar strengthening of adhesion on both substrates. However, this lack of adhesive specificity did not determine whether different cadherin-expressing cells would sort from each other, and the tendency to sort was not predictable by the extent of sequence diversity in their extracellular domains. These results show that cadherins are far more promiscuous in their adhesive-binding capacity than had been expected and that the ability to sort out must be determined by mechanisms other than simple adhesive-binding specificity.

Key Words: cadherins; adhesion; cell sorting; heterophilic; specificity


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