Abstract
The classical cadherins, definitive proteins of the cadherin superfamily, are characterized functionally by their ability to mediate calcium-dependent cell aggregation in vitro. To test hypothetical mechanisms of adhesion, we have constructed two mutants of the chicken E-cadherin protein, one with the highly conserved His-Ala-Val (HAV) sequence motif reversed to Val-Ala-His (VAH), the other lacking the first extracellular domain (EC1). The inversion of HAV to VAH has no effect on the capacity of E-cadherin to mediate adhesion. Deletion of EC1 completely eliminates the ability of E-cadherin to mediate homophilic adhesion, but the deletion mutant is capable of adhering heterophilically to both unmutated E-cadherin and to the HAV/VAH mutant. These results demonstrate that the conserved HAV sequence motif is not involved in cadherin-mediated adhesion as has been suggested previously and supports the idea that in the context of the cell surface, cadherin-mediated cell-cell adhesion involves an interaction of EC1 with other domains of the cadherin extracellular moiety and not the "linear zipper" model, which posits trans interactions only between EC1 on apposing cell surfaces.
Highlights
Classical cadherins were defined initially by their ability to mediate calcium-dependent cell-cell adhesion [1,2,3,4,5]
These results demonstrate that the conserved HAV sequence motif is not involved in cadherin-mediated adhesion as has been suggested previously and supports the idea that in the context of the cell surface, cadherin-mediated cell-cell adhesion involves an interaction of EC1 with other domains of the cadherin extracellular moiety and not the “linear zipper” model, which posits trans interactions only between EC1 on apposing cell surfaces
To characterize the role of the HAV motif and of the whole EC1 in adhesion we evaluated the capability of two mutant forms of E-cadherin to mediate adhesion in a set of well defined cell-cell aggregation assays
Summary
Classical cadherins were defined initially by their ability to mediate calcium-dependent cell-cell adhesion [1,2,3,4,5]. Adhesive strength is dependent on a cis interaction between cadherins of the same cell [23] mediated at least in part by the transmembrane domain [24]. These stable interactions can be rapidly disassembled or reorganized in response to extracellular signals such as growth factors [25] and can occur without extreme alterations in the makeup of the adhesive complex or the amount of complex at the junction [26]
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