Phosphoinositide 3-kinase p110? 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? 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? 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? also regulates the organization of focal adhesions and membrane localization of dystroglycan. Thus, we uncover a previously unrecognized role for p110? in epithelial cells in the orientation of the apico-basal axis and lumen formation.

SUBMITTER: Peng J 

PROVIDER: S-EPMC5094449 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature