Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile

• Published in: Biology open 2016-11, Vol.5 (11), p.1607-1619
• Main Authors: Klemmt, Petra A B, Resch, Eduard, Smyrek, Isabell, Engels, Knut, Stelzer, Ernst H K, Starzinski-Powitz, Anna
• Format: Article
• Language: English
• Subjects: Adherence junctions; AJAP1; Antibodies; E-cadherin; Gene expression; Human tissues; Internalization; Lactation; Localization; Mammary gland; Mammary glands; Proteins; Splice variants; Structure-function relationships; Tumor suppressor genes; Tumor suppressor protein; Tumors; β-Catenin
• ISSN: 2046-6390; 2046-6390
• DOI: 10.1242/bio.019463

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.