March8 is a member of a family of transmembrane E3 ubiquitin ligases that have been studied mostly for their role in the immune system. We find that March8 is expressed in the zebrafish egg and early embryo, suggesting a role in development. Both knock-down and overexpression of March8 leads to abnormal development. The phenotype of zebrafish embryos and Xenopus animal explants overexpressing March8 implicates impairment of cell adhesion as a cause of the effect. In zebrafish embryos and in cultured cells, overexpression of March8 leads to a reduction in the surface levels of E-cadherin, a major cell-cell adhesion molecule. Experiments in cell culture further show that E-cadherin can be ubiquitinated by March8. On the basis of these observations we suggest that March8 functions in the embryo to modulate the strength of cell adhesion by regulating the localization of E-cadherin.
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