title: Phosphoinositide 3-kinase p110δ 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 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.
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Peng
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Aline
authors.initials: A
authors.lastname: Awad
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Sokhavuth
authors.initials: S
authors.lastname: Sar
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Ola Hamze
authors.initials: OH
authors.lastname: Komaiha
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Romina
authors.initials: R
authors.lastname: Moyano
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Amel
authors.initials: A
authors.lastname: Rayal
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.|AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire, F-94800 Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, Brisbane, Queensland 4072, Australia.
authors.forename: Annette
authors.initials: A
authors.lastname: Shewan
authors.affiliation: Cell Signalling, UCL Cancer Institute, University College London, 72 Huntley Street London WC1E 6BT, UK.
authors.forename: Bart
authors.initials: B
authors.lastname: Vanhaesebroeck
authors.affiliation: Departments of Anatomy, and Biochemistry and Biophysics, University of California San Francisco, School of Medicine, 600 16th Street, San Francisco, CA 94143-2140.
authors.forename: Keith
authors.initials: K
authors.lastname: Mostov
authors.affiliation: Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France;-Inserm.|Unité 785, Villejuif, F-94800, France.
authors.forename: Ama
authors.initials: A
authors.lastname: Gassama-Diagne
mesh_terms: D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D058543:Class Ia Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D051419:Paxillin / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D016596:Vinculin / Q000378:metabolism
chemical_list: D051419:Paxillin; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D016596:Vinculin; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D058543:Class Ia Phosphatidylinositol 3-Kinase