Phosphatidylinositol 3'-kinase signalling supports cell height in established epithelial monolayers

Jeanes, Angela, Smutny, Michael, Leerberg, Joanne M. and Yap, Alpha S. (2009) Phosphatidylinositol 3'-kinase signalling supports cell height in established epithelial monolayers. Journal of Molecular Histology, 40 5-6: 395-405. doi:10.1007/s10735-010-9253-y

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Author Jeanes, Angela
Smutny, Michael
Leerberg, Joanne M.
Yap, Alpha S.
Title Phosphatidylinositol 3'-kinase signalling supports cell height in established epithelial monolayers
Journal name Journal of Molecular Histology   Check publisher's open access policy
ISSN 1567-2379
Publication date 2009-10-01
Year available 2010
Sub-type Article (original research)
DOI 10.1007/s10735-010-9253-y
Volume 40
Issue 5-6
Start page 395
End page 405
Total pages 11
Place of publication Dordrecht, The Netherlands
Publisher Kluwer Academic Publishers
Collection year 2011
Language eng
Formatted 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.
© 2010 Springer Science+Business Media B.V.
Keyword Epithelia
Cell height
Nonmuscle Myosin-II
Adhesive Contacts
Local Concentration
Tight Junctions
Actin Dynamics
Lipid Products
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Received: 17 December 2009 / Accepted: 31 January 2010 / Published online: 16 February 2010

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 28 Mar 2010, 10:03:18 EST