Document Detail

Rho GTP exchange factor ARHGEF11 regulates the integrity of epithelial junctions by connecting ZO-1 and RhoA-myosin II signaling.
MedLine Citation:
PMID:  22665792     Owner:  NLM     Status:  MEDLINE    
The organization of the apical junctional complex and its association with the cytoskeleton is essential for the function of epithelial cells. However, knowledge about the signaling pathways that regulate these processes is still fragmentary. Here we found that ARHGEF11, a member of the RGS-RhoGEF family, associates with tight junctions (TJs) by binding to ZO-1, but not to the highly homologous ZO-2, in polarized epithelial cells. In the early phases of cell-cell contact, ARHGEF11 was located at primordial adherens junctions, and then its localization was altered to TJs as epithelial polarity was established, much like ZO-1. Knockdown of ARHGEF11 reduced the phosphorylation of myosin light chain, retarding the assembly of cell-cell junctions and the development of the paracellular barrier. Furthermore, the simultaneous knockdown of ARHGEF11 and ZO-2 resulted in significant impairment of TJs and of the perijunctional actomyosin ring; similar defects arise when both ZO-1 and ZO-2 are depleted. These results suggest that ARHGEF11 mediates RhoA-myosin light chain signaling pathways at cell-cell junctions, functioning in cooperation with ZO-1, to regulate the paracellular barrier and the organization of the apical junctional complex and perijunctional actomyosin ring of epithelial cells.
Masahiko Itoh; Sachiko Tsukita; Yuji Yamazaki; Hiroyuki Sugimoto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-06-04
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-20     Completed Date:  2012-09-10     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9905-10     Citation Subset:  IM    
Department of Biochemistry, School of Medicine, Dokkyo Medical University, Tochigi 321-0293 Japan.
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MeSH Terms
Cadherins / metabolism
Epithelial Cells / metabolism
Guanine Nucleotide Exchange Factors / genetics,  physiology*
Membrane Proteins / metabolism*
Myosin Type II / metabolism*
Phosphoproteins / metabolism*
Signal Transduction*
Tight Junctions / metabolism
Zonula Occludens-1 Protein
rhoA GTP-Binding Protein / metabolism*
Reg. No./Substance:
0/ARHGEF11 protein, mouse; 0/Cadherins; 0/Guanine Nucleotide Exchange Factors; 0/Membrane Proteins; 0/Phosphoproteins; 0/Tjp1 protein, mouse; 0/Zonula Occludens-1 Protein; EC 3.6.1.-/Myosin Type II; EC GTP-Binding Protein

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