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© The Rockefeller University Press, 0021-9525/1999//351 $5.00
The Journal of Cell Biology, Volume 144, Number 2, , 1999 351-359

Regular Articles

Analysis of C-cadherin Regulation during Tissue Morphogenesis with an Activating Antibody



Yun Zhong, William M. Brieher, and Barry M. Gumbiner

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

The regulation of cadherin-mediated adhesion at the cell surface underlies several morphogenetic processes. To investigate the role of cadherin regulation in morphogenesis and to begin to analyze the molecular mechanisms of cadherin regulation, we have screened for monoclonal antibodies (mAbs) that allow us to manipulate the adhesive state of the cadherin molecule.

Xenopus C-cadherin is regulated during convergent extension movements of gastrulation. Treatment of animal pole tissue explants (animal caps) with the mesoderm-inducing factor activin induces tissue elongation and decreases the strength of C-cadherin–mediated adhesion between blastomeres (Brieher, W.M., and B.M. Gumbiner. 1994. J. Cell Biol. 126:519–527). We have generated a mAb to C-cadherin, AA5, that restores strong adhesion to activin-treated blastomeres. This C-cadherin activating antibody strongly inhibits the elongation of animal caps in response to activin without affecting mesodermal gene expression. Thus, the activin-induced decrease in C-cadherin adhesive activity appears to be required for animal cap elongation.

Regulation of C-cadherin and its activation by mAb AA5 involve changes in the state of C-cadherin that encompass more than changes in its homophilic binding site. Although mAb AA5 elicited a small enhancement in the functional activity of the soluble C-cadherin ectodomain (CEC1-5), it was not able to restore cell adhesion activity to mutant C-cadherin lacking its cytoplasmic tail. Furthermore, activin treatment regulates the adhesion of Xenopus blastomeres to surfaces coated with two other anti–C-cadherin mAbs, even though these antibodies probably do not mediate adhesion through a normal homophilic binding mechanism. Moreover, mAb AA5 restores strong adhesion to these antibodies. mAb AA5 only activates adhesion of blastomeres to immobilized CEC1-5 when it binds to C-cadherin on the cell surface. It does not work when added to CEC1-5 on the substrate. Together these findings suggest that the regulation of C-cadherin by activin and its activation by mAb AA5 involve changes in its cellular organization or interactions with other cell components that are not intrinsic to the isolated protein.

Key Words: adhesion • activin • C-cadherin • morphogenesis • Xenopus

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

This research was funded by National Institutes of Health grant GM52717 awarded to B.M. Gumbiner and the Cancer Center Support grant NCI-P30-CA-08748 to the Memorial Sloan-Kettering Cancer Center.


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