Citation
- Authors: Peng, J., Awad, A., Sar, S., Hamze Komaiha, O., Moyano, R., Rayal, A., Samuel, D., Shewan, A., Vanhaesebroeck, B., Mostov, K., Gassama-Diagne, A.
- Year: 2015
- Journal: Nat Commun 6 5937
- Applications: in vitro / DNA, siRNA / jetPRIME
- Cell type: MDCK
Description: Canine kidney epithelial cells
Abstract
Signalling triggered by adhesion to the extracellular matrix plays a key role in the spatial orientation of epithelial polarity and formation of lumens in glandular tissues. Phosphoinositide 3-kinase signalling in particular is known to influence the polarization process during epithelial cell morphogenesis. Here, using Madin-Darby canine kidney epithelial cells grown in 3D culture, we show that the p110delta isoform of phosphoinositide 3-kinase co-localizes with focal adhesion proteins at the basal surface of polarized cells. Pharmacological, siRNA- or kinase-dead-mediated inhibition of p110delta impair the early stages of lumen formation, resulting in inverted polarized cysts, with no laminin or type IV collagen assembly at cell/extracellular matrix contacts. p110delta also regulates the organization of focal adhesions and membrane localization of dystroglycan. Thus, we uncover a previously unrecognized role for p110delta in epithelial cells in the orientation of the apico-basal axis and lumen formation.