Phosphoinositide 3-kinase p110δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization
Juan Peng,
Aline Awad,
Sokhavuth Sar,
Ola Hamze Komaiha,
Romina Moyano,
Amel Rayal,
Didier Samuel,
Annette Shewan,
Bart Vanhaesebroeck,
Keith Mostov and
Ama Gassama-Diagne ()
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Juan Peng: Université Paris-Sud
Aline Awad: Université Paris-Sud
Sokhavuth Sar: Université Paris-Sud
Ola Hamze Komaiha: Université Paris-Sud
Romina Moyano: Université Paris-Sud
Amel Rayal: Université Paris-Sud
Didier Samuel: Université Paris-Sud
Annette Shewan: School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia,
Bart Vanhaesebroeck: Cell Signalling, UCL Cancer Institute, University College London
Keith Mostov: University of California San Francisco, School of Medicine
Ama Gassama-Diagne: Université Paris-Sud
Nature Communications, 2015, vol. 6, issue 1, 1-16
Abstract:
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.
Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6937
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DOI: 10.1038/ncomms6937
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