Phosphoinositide 3-kinase p110 δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization

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 p110 δ 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 p110 δ 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. p110 δ also regulates the organization of focal adhesions and membrane localization of dystroglycan. Thus, we uncover a previously unrecognized role for p110 δ in epithelial cells in the orientation of the apico-basal axis and lumen formation.