PAR-6 regulates aPKC activity in a novel way and mediates cell-cell contact-induced formation of the epithelial junctional complex.
BACKGROUND
PAR-6, aPKC and PAR-3 are polarity proteins that co-operate in the establishment of cell polarity in Caenorhabditis elegans and Drosophila embryos. We have recently shown that mammalian aPKC is required for the formation of the epithelia-specific cell-cell junctional structure. We have also revealed that a mammalian PAR-6 forms a ternary complex with aPKC and ASIP/PAR-3, and localizes at the most apical end of the junctional complex in epithelial cells.


RESULTS
The ternary complex formation and junctional co-localization of PAR-6 with aPKC and ASIP/PAR-3 are observed during the early stage of epithelial cell polarization. In addition, over-expression of the PAR-6 mutant with CRIB/PDZ domain in MDCK cells disturbs the cell-cell contact-induced junctional localization of tight junction proteins, as well as inhibiting TER development. Furthermore, the binding of Cdc42:GTP to the CRIB/PDZ domain of PAR-6 enhances the kinase activity of PAR-6-bound aPKC. Detailed analyses suggest that the binding of PAR-6 to aPKC has the intrinsic potential to activate aPKC, which is only released when Cdc42:GTP binds to the CRIB/PDZ domain.


CONCLUSIONS
The results indicate the involvement of PAR-6 in the aPKC function which is required for the cell-cell adhesion-induced formation of epithelial junctional structures, possibly through the cooperative regulation of aPKC activity with Cdc42.
Yamanaka
T
T
Department of Molecular Biology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan.
Horikoshi
Y
Y
Suzuki
A
A
Sugiyama
Y
Y
Kitamura
K
K
Maniwa
R
R
Nagai
Y
Y
Yamashita
A
A
Hirose
T
T
Ishikawa
H
H
Ohno
S
S
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002450:Cell Communication; D018797:Cell Cycle Proteins; D002460:Cell Line; D002461:Cell Line, Transformed; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D015801:Helminth Proteins / Q000502:physiology; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D009154:Mutation; D011485:Protein Binding; D011493:Protein Kinase C / Q000502:physiology*; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D015801:Helminth Proteins; C115084:Pard3 protein, mouse; D011506:Proteins; C512642:par-6 protein, C elegans; D006160:Guanosine Triphosphate; C115015:PKC-3 protein; D011493:Protein Kinase C; D020764:cdc42 GTP-Binding Protein