Snail Destabilizes Cell Surface Crumbs3a

Traffic. 2012 Aug;13(8):1170-85. doi: 10.1111/j.1600-0854.2012.01376.x. Epub 2012 May 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Membrane / metabolism
  • Dogs
  • Epithelial Cells / metabolism
  • Epithelial-Mesenchymal Transition
  • Glycosylation
  • Humans
  • Membrane Glycoproteins / metabolism*
  • Protein Processing, Post-Translational
  • Protein Stability
  • Snail Family Transcription Factors
  • Tight Junctions / metabolism
  • Transcription Factors / metabolism*

Substances

  • CRB3 protein, human
  • Membrane Glycoproteins
  • Snail Family Transcription Factors
  • Transcription Factors