RRC ID 2054
Author Mishima A, Suzuki A, Enaka M, Hirose T, Mizuno K, Ohnishi T, Mohri H, Ishigatsubo Y, Ohno S.
Title Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK cells.
Journal Genes Cells
Abstract BACKGROUND:PAR-3 is one of the PAR proteins, previously named ASIP, which are indispensable for the establishment of cell polarity in the embryo as well as differentiated epithelial cells. In mammalian epithelial cells, it forms a ternary complex with aPKC and PAR-6, and is localized to the tight junction that has been suggested as being important for creating cell polarity.
RESULTS:To gain insights into the mode of PAR-3 function in mammalian epithelial cells, we examined the effect of PAR-3 over-expression in MDCK cells. Although exogenous PAR-3-expression does not affect the epithelial polarity of confluent cells, it drastically transforms the morphology of cells at low density into a fibroblastic form with developed membrane protrusions. Time-lapse observations have revealed that PAR-3 over-expressing cells show intense motility, even after they have assembled into loose colonies, suggesting that the contact-mediated inhibition of cell migration (CIM) is suppressed. The expressions of E-cadherin and vimentin do not change with PAR-3 over-expression, suggesting that exogenous PAR-3 only disturbs the endogenous equilibrium of cellular states between a fundamental fibroblastic structure and an epithelial one. The co-expression of a dominant negative mutant of Rac1 and the addition of nocodazole strongly antagonize the effect of PAR-3 over-expression, suggesting the involvement of Rac1 activation and microtubule polymerizations.
CONCLUSIONS:: The data presented here suggest an intriguing link between the contact-mediated inhibition of cell migration and the regulation of cell polarity. The putative PAR-3 activities demonstrated here may function endogenously in the epithelial cell polarization process by being sequestered from the cytosol to the cell-cell junctional regions with aPKC and PAR-6 upon cell-cell adhesion.
Volume 7(6)
Pages 581-96
Published 2002-6-1
DOI 10.1046/j.1365-2443.2002.00540.x
PII 540
PMID 12059961
MeSH Actins / metabolism Animals Binding Sites Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / physiology* Cell Communication Cell Count Cell Line Cell Migration Inhibition Cell Movement / physiology* Microscopy, Video Microtubules / physiology Mutation Protein Serine-Threonine Kinases Transfection cdc42 GTP-Binding Protein / genetics cdc42 GTP-Binding Protein / physiology rac1 GTP-Binding Protein / genetics rac1 GTP-Binding Protein / physiology
IF 1.655
Times Cited 17
DNA material AxCANLacZ (RDB1749)