Snail destabilizes cell surface Crumbs3a.

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Jennifer L HarderBen Margolis

Abstract

During epithelial to mesenchymal transition (EMT), cells modulate expression of proteins resulting in loss of apical-basal polarity. Effectors of this EMT switch target the polarity protein Crumbs3a, a small transmembrane protein that is essential for generation of the apical membrane and tight junctions of mammalian epithelial cells. We previously showed that the Crumbs3 gene is a direct target of transcriptional regulation by Snail, a potent inducer of EMT. However, Snail has also been shown to have multiple non-transcriptional roles, including regulation of cell adhesion, proliferation and survival. Using SNAP-tag labeling, we determined that cell surface Crumbs3a has a half-life of approximately 3 h and that this cell surface half-life is significantly reduced when EMT is induced by Snail. We further observe that Snail induces differential glycosylation of Crumbs3a, including sialylation, suggesting a mechanism by which Crumbs3a may be destabilized. These results indicate that Crumbs3a is a post-translational target of Snail, in addition to being a transcriptional target. We conclude that Snail's ability to post-translationally modify and destabilize Crumbs3a augments the depolarizing process of EMT.

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Citations

Oct 28, 2015·The Journal of Cell Biology·Emily H StoopsMichael J Caplan
Mar 16, 2016·Biochimica Et Biophysica Acta·Ivona DjuricThomas Weide
Sep 26, 2015·Scientific Reports·Antonio E PaniaguaConcepción Lillo
Feb 24, 2015·Nature Cell Biology·Alejo E Rodríguez-FraticelliFernando Martín-Belmonte
Jun 16, 2017·Cellular Microbiology·Rocio TapiaGail A Hecht
Oct 30, 2013·Molecular and Cellular Biology·Eileen L WhitemanBen Margolis
Jun 4, 2014·The Journal of Biological Chemistry·Darya KarabashevaJulie G Donaldson
Apr 4, 2019·Molecular Biology of the Cell·Christina M Van ItallieJames Melvin Anderson
Jul 27, 2018·Cancer Prevention Research·Melissa L NewMeredith A Tennis

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