Document Detail


Cingulin regulates claudin-2 expression and cell proliferation through the small GTPase RhoA.
MedLine Citation:
PMID:  16723500     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In mouse embryoid bodies, mutation of the tight junction protein cingulin results in changes in gene expression. Here, we studied the function of cingulin using a gene silencing approach in Madin-Darby canine kidney (MDCK) cells. Cingulin-depleted cells show higher protein and mRNA levels of claudin-2 and ZO-3, increased RhoA activity, activation of G1/S phase transition, and increased cell density. The effects of cingulin depletion on claudin-2 expression, cell proliferation, and density are reversed by coexpression of either a dominant-negative form of RhoA (RhoAN19) or the Rho-inhibiting enzyme C3 transferase. However, the increase in ZO-3 protein and mRNA levels is not reversed by inhibition of either RhoA, p38, extracellular signal-regulated kinase (ERK), or c-Jun NH2-terminal kinase (JNK), suggesting that cingulin modulates ZO-3 expression by a different mechanism. JNK is implicated in the regulation of claudin-2 levels independently of cingulin depletion and RhoA activity, indicating distinct roles of RhoA- and JNK-dependent pathways in the control of claudin-2 expression. Finally, cingulin depletion does not significantly alter the barrier function of monolayers and the overall molecular organization of tight junctions. These results provide novel insights about the mechanisms of cingulin function and the signaling pathways controlling claudin-2 expression in MDCK cells.
Authors:
Laurent Guillemot; Sandra Citi
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-24
Journal Detail:
Title:  Molecular biology of the cell     Volume:  17     ISSN:  1059-1524     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-28     Completed Date:  2006-10-02     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3569-77     Citation Subset:  IM    
Affiliation:
Department of Molecular Biology, University of Geneva, CH-1211 Geneva, Switzerland.
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MeSH Terms
Descriptor/Qualifier:
Animals
Carrier Proteins / metabolism
Cell Count
Cell Movement
Cell Proliferation*
Cells, Cultured
Dogs
Epithelial Cells / cytology
G1 Phase
Humans
JNK Mitogen-Activated Protein Kinases / metabolism
Membrane Proteins / metabolism*
Mice
Microfilament Proteins / deficiency,  metabolism*
Protein Transport
S Phase
Tight Junctions / metabolism
Up-Regulation / genetics
Zonula Occludens Proteins
rhoA GTP-Binding Protein / metabolism*
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Membrane Proteins; 0/Microfilament Proteins; 0/Zonula Occludens Proteins; EC 2.7.11.24/JNK Mitogen-Activated Protein Kinases; EC 3.6.5.2/rhoA GTP-Binding Protein
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