1. Phosphoinositide 3-kinase p110δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization
- Author
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Peng, Juan, Awad, Aline, Sar, Sokhavuth, Hamze Komaiha, Ola, Moyano, Romina, Rayal, Amel, Samuel, Didier, Shewan, Annette, Vanhaesebroeck, Bart, Mostov, Keith, and Gassama-Diagne, Ama
- Subjects
Biochemistry and Cell Biology ,Biological Sciences ,Stem Cell Research ,Kidney Disease ,Stem Cell Research - Nonembryonic - Non-Human ,1.1 Normal biological development and functioning ,Underpinning research ,Animals ,Base Sequence ,Cell Adhesion ,Cell Membrane ,Cell Polarity ,Class Ia Phosphatidylinositol 3-Kinase ,Collagen ,Dogs ,Epithelial Cells ,Extracellular Matrix ,HeLa Cells ,Humans ,Madin Darby Canine Kidney Cells ,Microscopy ,Fluorescence ,Molecular Sequence Data ,Paxillin ,Phosphatidylinositol 3-Kinases ,Protein Isoforms ,RNA ,Small Interfering ,Signal Transduction ,Vinculin ,Hela 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 p110δ 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 p110δ 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. p110δ also regulates the organization of focal adhesions and membrane localization of dystroglycan. Thus, we uncover a previously unrecognized role for p110δ in epithelial cells in the orientation of the apico-basal axis and lumen formation.
- Published
- 2015