title: Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile.
abstract: Shrew-1, also called AJAP1, is a transmembrane protein associated with E-cadherin-mediated adherence junctions and a putative tumor suppressor. Apart from its interaction with β-catenin and involvement in E-cadherin internalization, little structure or function information exists. Here we explored shrew-1 expression during postnatal differentiation of mammary gland as a model system. Immunohistological analyses with antibodies against either the extracellular or the cytoplasmic domains of shrew-1 consistently revealed the expression of full-length shrew-1 in myoepithelial cells, but only part of it in luminal cells. While shrew-1 localization remained unaltered in myoepithelial cells, nuclear localization occurred in luminal cells during lactation. Based on these observations, we identified two unknown shrew-1 transcript variants encoding N-terminally truncated proteins. The smallest shrew-1 protein lacks the extracellular domain and is most likely the only variant present in luminal cells. RNA analyses of human tissues confirmed that the novel transcript variants of shrew-1 exist in vivo and exhibit a differential tissue expression profile. We conclude that our findings are essential for the understanding and interpretation of future functional and interactome analyses of shrew-1 variants.
authors.affiliation: Institute of Cell Biology and Neuroscience, Department of Molecular Cell Biology and Human Genetics, Goethe Universität Frankfurt am Main, Max-von-Laue-Straße 13, Frankfurt am Main D-60438, Germany.
authors.forename: Petra A B
authors.initials: PA
authors.lastname: Klemmt
authors.affiliation: Institute of Cell Biology and Neuroscience, Department of Molecular Cell Biology and Human Genetics, Goethe Universität Frankfurt am Main, Max-von-Laue-Straße 13, Frankfurt am Main D-60438, Germany.
authors.forename: Eduard
authors.initials: E
authors.lastname: Resch
authors.affiliation: Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe Universität Frankfurt am Main, Max-von-Laue-Straße 15, Frankfurt am Main D-60438, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Smyrek
authors.affiliation: Center for Pathology, Cytology and Molecular Pathology, Neuss D-41462, Germany.
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
authors.affiliation: Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe Universität Frankfurt am Main, Max-von-Laue-Straße 15, Frankfurt am Main D-60438, Germany.
authors.forename: Ernst H K
authors.initials: EH
authors.lastname: Stelzer
authors.affiliation: Institute of Cell Biology and Neuroscience, Department of Molecular Cell Biology and Human Genetics, Goethe Universität Frankfurt am Main, Max-von-Laue-Straße 13, Frankfurt am Main D-60438, Germany starzinski-powitz@bio.uni-frankfurt.de.
authors.forename: Anna
authors.identifier: http://orcid.org/0000-0003-4552-4193
authors.initials: A
authors.lastname: Starzinski-Powitz
keywords: AJAP1; Adherence junctions; Lactation; Mammary gland; Splice variants; Tumor suppressor protein