Document Detail


Snail destabilizes cell surface Crumbs3a.
MedLine Citation:
PMID:  22554228     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Jennifer L Harder; Eileen L Whiteman; Jay N Pieczynski; Chia-Jen Liu; Ben Margolis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-05-28
Journal Detail:
Title:  Traffic (Copenhagen, Denmark)     Volume:  13     ISSN:  1600-0854     ISO Abbreviation:  Traffic     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-11-19     Revised Date:  2013-08-14    
Medline Journal Info:
Nlm Unique ID:  100939340     Medline TA:  Traffic     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  1170-85     Citation Subset:  IM    
Copyright Information:
© 2012 John Wiley & Sons A/S.
Affiliation:
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cell Membrane / metabolism
Dogs
Epithelial Cells / metabolism
Epithelial-Mesenchymal Transition
Glycosylation
Humans
Membrane Glycoproteins / metabolism*
Protein Processing, Post-Translational
Protein Stability
Tight Junctions / metabolism
Transcription Factors / metabolism*
Grant Support
ID/Acronym/Agency:
DK020572/DK/NIDDK NIH HHS; F32GM079906/GM/NIGMS NIH HHS; R01 DK069605/DK/NIDDK NIH HHS; R01DK058208/DK/NIDDK NIH HHS; R01DK069605/DK/NIDDK NIH HHS; T32DK007378/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/CRB3 protein, human; 0/Membrane Glycoproteins; 0/Transcription Factors; 0/snail family transcription factors
Comments/Corrections

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