Journal
TRAFFIC
Volume 13, Issue 8, Pages 1170-1185Publisher
WILEY
DOI: 10.1111/j.1600-0854.2012.01376.x
Keywords
apical-basal; Crumbs; EMT; epithelial; glycosylation; polarity; sialylation; Snail
Categories
Funding
- National Institutes of Health (NIH) [R01DK069605, R01DK058208]
- National Kidney Foundation
- NIH Institutional Postdoctoral Kirschstein National Research Service [T32DK007378]
- NIH Individual Postdoctoral Kirschstein National Research Service [F32GM079906]
- National Institute of Diabetes and Digestive and Kidney Diseases [DK020572]
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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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