Cadherin engagement regulates Rho family GTPases Journal Article


Authors: Noren, N. K.; Niessen, C. M.; Gumbiner, B. M.; Burridge, K.
Article Title: Cadherin engagement regulates Rho family GTPases
Abstract: The formation of cell-cell adherens junctions is a cadherin-mediated process associated with reorganization of the actin cytoskeleton. Because Rho family GTPases regulate actin dynamics, we investigated whether cadherin-mediated adhesion regulates the activity of RhoA, Rac1, and Cdc42. Confluent epithelial cells were found to have elevated Racl and Cdc42 activity but decreased RhoA activity when compared with low density cultures. Using a calcium switch method to manipulate junction assembly, we found that induction of cell-cell junctions increased Racl activity, and this was inhibited by E-cadherin function-blocking antibodies. Using the same calcium switch procedure, we found little effect on RhoA activity during the first hour of junction assembly. However, over several hours, RhoA activity significantly decreased. To determine whether these effects are mediated directly through cadherins or indirectly through engagement of other surface proteins downstream from junction assembly, we used a model system in which cadherin engagement is induced without cell-cell contact. For these experiments, Chinese hamster ovary cells expressing C-cadherin were plated on the extracellular domain of C-cadherin immobilized on tissue culture plates. Whereas direct cadherin engagement did not stimulate Cdc42 activity, it strongly inhibited RhoA activity but increased Rac1 activity. Deletion of the C-cadherin cytoplasmic domain abolished these effects.
Keywords: nonhuman; protein domain; proteins; animal cell; mouse; animal; metabolism; animals; mice; cells, cultured; protein assembly; cell line; protein binding; calcium; time; time factors; animalia; chemistry; enzyme regulation; cell culture; dog; dogs; membrane protein; epithelium cell; epithelial cells; biochemistry; cadherin; cell adhesion; cell communication; cadherins; rho guanine nucleotide binding protein; rho gtp-binding proteins; cell strain 3t3; protein cdc42; rac protein; 3t3 cells; gtp phosphohydrolases; cho cell; cho cells; cricetinae; cricetulus griseus; cells; rho factor; guanosine triphosphatase; calcium transport; cytoarchitecture; immobilized cell; actin filament; rac1 protein; hamster; cdc42 gtp-binding protein; rac1 gtp-binding protein; cell-cell junctions; humans; human; priority journal; article
Journal Title: Journal of Biological Chemistry
Volume: 276
Issue: 36
ISSN: 0021-9258
Publisher: American Society for Biochemistry and Molecular Biology  
Date Published: 2001-09-07
Start Page: 33305
End Page: 33308
Language: English
DOI: 10.1074/jbc.C100306200
PUBMED: 11457821
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 21 May 2015 -- Source: Scopus
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