title: Snail destabilizes cell surface Crumbs3a.
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.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Harder
authors.forename: Eileen L
authors.initials: EL
authors.lastname: Whiteman
authors.forename: Jay N
authors.initials: JN
authors.lastname: Pieczynski
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Liu
authors.forename: Ben
authors.initials: B
authors.lastname: Margolis
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D006031:Glycosylation; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D055550:Protein Stability; D000071250:Snail Family Transcription Factors; D019108:Tight Junctions / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C472002:CRB3 protein, human; D008562:Membrane Glycoproteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors