Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarised epithelial cells

While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910 bp cDNA encoding a novel putative 411 amino acid integral membrane protein which we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides which labelled a protein of ca. 48 kDa in extracts of shrew-1 mRNA positive tissue and also detected ectopically expressed shrew-1. Expression of epitope-tagged shrew-1 in epithelial cells and analysis by surface biotinylation and immunoblots demonstrated that shrew-1 is indeed a transmembrane protein. Shrew-1 is able to target to E-cadherin-mediated adherens junctions and interact with the E-cadherin-catenin complex in polarised MCF7 and MDCK cells, but not with the N-cadherin-catenin complex in non-polarised epithelial cells. Direct interaction of shrew-1 with β-catenin in in vitro pulldown assay suggests that β-catenin might be one of the proteins that targets and/or retains shrew-1 in the adherens junctions. Interestingly, shrew-1 was partially translocated in response to scatter factor (ligand of receptor tyrosine kinase cmet) from the plasma membrane to the cytoplasm where it still colocalised with endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of adherens junctions, interacting with E-cadherin-β-catenin complexes in polarised epithelial cells.