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Originally published as MBC in Press, 10.1091/mbc.E03-05-0281 on October 31, 2003

Vol. 15, Issue 1, 397-406, January 2004

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Novel Membrane Protein shrew-1 Targets to Cadherin-Mediated Junctions in Polarized Epithelial Cells

Sanita Bharti *, Heike Handrow-Metzmacher *, Silvia Zickenheiner *, Andreas Zeitvogel *, Rudolf Baumann {dagger}, and Anna Starzinski-Powitz * {ddagger}

* Humangenetik fuer Biologen, Johann Wolfgang Goethe-Universität, D-60054 Frankfurt, Germany; {dagger} Bürgerhospital Frankfurt, Section of Gynecological Endocrinology and Fertility Surgery, D-60318 Frankfurt, Germany

Submitted May 7, 2003; Revised September 1, 2003; Accepted September 9, 2003
Monitoring Editor: Mary Beckerle

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 ~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.


Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E03–05–0281. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E03-05-0281.

{ddagger} Corresponding author. E-mail address: starzinski-powitz{at}em.uni-frankfurt.de.




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