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

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 s...

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Main Authors: Petra A. B. Klemmt, Eduard Resch, Isabell Smyrek, Knut Engels, Ernst H. K. Stelzer, Anna Starzinski-Powitz
Format: Article
Language:English
Published: The Company of Biologists 2016-11-01
Series:Biology Open
Subjects:
Online Access:http://bio.biologists.org/content/5/11/1607
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author Petra A. B. Klemmt
Eduard Resch
Isabell Smyrek
Knut Engels
Ernst H. K. Stelzer
Anna Starzinski-Powitz
author_facet Petra A. B. Klemmt
Eduard Resch
Isabell Smyrek
Knut Engels
Ernst H. K. Stelzer
Anna Starzinski-Powitz
author_sort Petra A. B. Klemmt
collection DOAJ
description 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.
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spelling doaj.art-a3cd5917bbd6477ba61ab1818a3e52952022-12-21T22:52:23ZengThe Company of BiologistsBiology Open2046-63902016-11-015111607161910.1242/bio.019463019463Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profilePetra A. B. Klemmt0Eduard Resch1Isabell Smyrek2Knut Engels3Ernst H. K. Stelzer4Anna Starzinski-Powitz5 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 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 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 Center for Pathology, Cytology and Molecular Pathology, Neuss D-41462, Germany 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 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 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.http://bio.biologists.org/content/5/11/1607AJAP1Mammary glandLactationSplice variantsAdherence junctionsTumor suppressor protein
spellingShingle Petra A. B. Klemmt
Eduard Resch
Isabell Smyrek
Knut Engels
Ernst H. K. Stelzer
Anna Starzinski-Powitz
Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile
Biology Open
AJAP1
Mammary gland
Lactation
Splice variants
Adherence junctions
Tumor suppressor protein
title Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile
title_full Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile
title_fullStr Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile
title_full_unstemmed Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile
title_short Alternative exon usage creates novel transcript variants of tumor suppressor SHREW-1 gene with differential tissue expression profile
title_sort alternative exon usage creates novel transcript variants of tumor suppressor shrew 1 gene with differential tissue expression profile
topic AJAP1
Mammary gland
Lactation
Splice variants
Adherence junctions
Tumor suppressor protein
url http://bio.biologists.org/content/5/11/1607
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