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Phosphatidylinositol 3′-kinase signalling supports cell height in established epithelial monolayers
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Jeanes, Angela, Smutny, Michael, Leerberg, Joanne M. and Yap, Alpha S. (2010) Phosphatidylinositol 3′-kinase signalling supports cell height in established epithelial monolayers. Journal of Molecular Histology, 40 (5-6). pp. 395-405. doi:10.1007/s10735-010-9253-y ISSN 1567-2379.
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Official URL: http://dx.doi.org/10.1007/s10735-010-9253-y
Abstract
Cell–cell interactions influence epithelial morphogenesis through an interplay between cell adhesion, trafficking and the cytoskeleton. These cellular processes are coordinated, often by cell signals found at cell–cell contacts. One such contact-based signal is the phosphatidylinositol 3′-kinase (PI3-kinase; PI3K) pathway. PI3-kinase is best understood for its role in mitogenic signalling, where it regulates cell survival, proliferation and differentiation. Its precise morphogenetic impacts in epithelia are, in contrast, less well-understood. Using phosphoinositide-specific biosensors we confirmed that E-cadherin-based cell–cell contacts are enriched in PIP3, the principal product of PI3-kinase. We then used pharmacologic inhibitors to assess the morphogenetic impact of PI3-kinase in MDCK and MCF7 monolayers. We found that inhibiting PI3-kinase caused a reduction in epithelial cell height that was reversible upon removal of the drugs. This was not attributable to changes in E-cadherin expression or homophilic adhesion. Nor were there detectable changes in cell polarity. While Myosin II has been implicated in regulating keratinocyte height, we found no effect of PI3-kinase inhibition on apparent Myosin II activity; nor did direct inhibition of Myosin II alter epithelial height. Instead, in pursuing signalling pathways downstream of PI3-kinase we found that blocking Rac signalling, but not mTOR, reduced epithelial cell height, as did PI3-kinase inhibition. Overall, our findings suggest that PI3-kinase exerts a major morphogenetic impact in simple cultured epithelia through preservation of cell height. This is independent of potential effects on adhesion or polarity, but may occur through PI3-kinase-stimulated Rac signaling.
| Item Type: | Journal Article | ||||
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| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Cell & Developmental Biology Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
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| Journal or Publication Title: | Journal of Molecular Histology | ||||
| Publisher: | Springer | ||||
| ISSN: | 1567-2379 | ||||
| Official Date: | 16 February 2010 | ||||
| Dates: |
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| Volume: | 40 | ||||
| Number: | 5-6 | ||||
| Page Range: | pp. 395-405 | ||||
| DOI: | 10.1007/s10735-010-9253-y | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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