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J. Cell Biol.,
Volume 144, Number 2, January 25, 1999 351-359
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.
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