title: Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK 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.
authors.affiliation: Department of Molecular Biology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Mishima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Makiko
authors.initials: M
authors.lastname: Enaka
authors.forename: Tomonori
authors.initials: T
authors.lastname: Hirose
authors.forename: Keiko
authors.initials: K
authors.lastname: Mizuno
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Ohnishi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mohri
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ishigatsubo
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002450:Cell Communication; D002452:Cell Count; D002460:Cell Line; D002464:Cell Migration Inhibition; D002465:Cell Movement / Q000502:physiology*; D018715:Microscopy, Video; D008870:Microtubules / Q000502:physiology; D009154:Mutation; D017346:Protein Serine-Threonine Kinases; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000502:physiology
chemical_list: D000199:Actins; D029742:Caenorhabditis elegans Proteins; C097238:PAR-3 protein, C elegans; D017346:Protein Serine-Threonine Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein