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

Mol Biol Cell. 2004 Jan;15(1):397-406. doi: 10.1091/mbc.e03-05-0281. Epub 2003 Oct 31.

Abstract

While searching for potential candidate molecules relevant for the pathogenesis of endometriosis, we discovered a 2910-base pair cDNA encoding a novel putative 411-amino acid integral membrane protein that we called shrew-1. The putative open-reading frame was confirmed with antibodies against shrew-1 peptides that labeled a protein of approximately 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 polarized MCF7 and Madin-Darby canine kidney cells, but not with the N-cadherin-catenin complex in nonpolarized epithelial cells. Direct interaction of shrew-1 with beta-catenin in in vitro pull-down assay suggests that beta-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 c-met) from the plasma membrane to the cytoplasm where it still colocalized with endogenous E-cadherin. In summary, we introduce shrew-1 as a novel component of adherens junctions, interacting with E-cadherin-beta-catenin complexes in polarized epithelial cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / metabolism*
  • Amino Acid Sequence
  • Animals
  • Cadherins / metabolism*
  • Cell Adhesion Molecules
  • Cell Polarity / physiology
  • Cells, Cultured
  • Cloning, Molecular
  • Cytoskeletal Proteins / metabolism*
  • Dogs
  • Endometriosis / metabolism
  • Epithelial Cells / metabolism*
  • Female
  • Gene Expression Profiling
  • Humans
  • Membrane Proteins / metabolism*
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Trans-Activators / metabolism*
  • beta Catenin

Substances

  • AJAP1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Membrane Proteins
  • Trans-Activators
  • beta Catenin