PAR‐6 regulates aPKC activity in a novel way and mediates cell‐cell contact‐induced formation of the epithelial junctional complex
Abstract
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 . Conclusion 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 .
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Activation of the Par3/Par6/aPKC complex depends on the formation of cell-cell contacts.
“Its activation depends on the formation of cell-cell contacts (Yamanaka et al, 2001) and Armadillo, the fly b-catenin homologue, is important for proper localization of this complex in Drosophila (Bilder et al, 2003;Tanentzapf and Tepass, 2003).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Yamanaka et al, 2001
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- Authors
- Yamanaka, T., Horikoshi, Y., Suzuki, A., Sugiyama, Y., Kitamura, K., Maniwa, R., Nagai, Y., Yamashita, A., Hirose, T., Ishikawa, H., & Ohno, S.
- Affiliations
- Yokohama City University (JP)
- Corresponding author
- Ohno, Shigeo
- ORCID
- Venue
- Genes to Cells
- Publisher
- Wiley
- Published
- 2001-08
- Volume
- 6
- Issue
- 8
- Pages
- 721-731
- ISSN
- 1356-9597 (ISSN-L)
- 1365-2443
- OpenAlex
- W1977245174
- Cited by
- 306
- References
- 47
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4 · 2023: 2 · 2022: 7 · 2021: 7 · 2020: 13 · 2019: 8 · 2018: 9 · 2017: 13 · 2016: 8 · 2015: 11 · 2014: 19 · 2013: 16 · 2012: 16
- FWCI
- 6.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genes to Cells (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- Par6, atypical protein kinase C, cell polarity, epithelial junctions, tight junctions, cell-cell contact, Cdc42, ternary complex, MDCK cells, transepithelial electrical resistance, cell adhesion
- MeSH terms
- Animals, Carrier Proteins, Cell Adhesion, Cell Communication, Cell Line, Cell Line, Transformed, Epithelial Cells, Guanosine Triphosphate, Humans, Intercellular Junctions, Mutation, Protein Binding, Protein Kinase C, Proteins, Transfection, Signal Transduction, Helminth Proteins, Cell Adhesion Molecules, Cell Polarity, Caenorhabditis elegans, Cell Cycle Proteins, COS Cells, cdc42 GTP-Binding Protein, Caenorhabditis elegans Proteins, Adaptor Proteins, Signal Transducing
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