Author
Listed:
- Juan Peng
(Université Paris-Sud
Inserm Unité 785)
- Aline Awad
(Université Paris-Sud
Inserm Unité 785)
- Sokhavuth Sar
(Université Paris-Sud
Inserm Unité 785)
- Ola Hamze Komaiha
(Université Paris-Sud
Inserm Unité 785)
- Romina Moyano
(Université Paris-Sud
Inserm Unité 785)
- Amel Rayal
(Université Paris-Sud
Inserm Unité 785)
- Didier Samuel
(Université Paris-Sud
Inserm Unité 785
AP-HP Hôpital Paul Brousse, Centre Hépato-Biliaire)
- 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
Inserm Unité 785)
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.
Suggested Citation
Juan Peng & Aline Awad & Sokhavuth Sar & Ola Hamze Komaiha & Romina Moyano & Amel Rayal & Didier Samuel & Annette Shewan & Bart Vanhaesebroeck & Keith Mostov & Ama Gassama-Diagne, 2015.
"Phosphoinositide 3-kinase p110δ promotes lumen formation through the enhancement of apico-basal polarity and basal membrane organization,"
Nature Communications, Nature, vol. 6(1), pages 1-16, May.
Handle:
RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms6937
DOI: 10.1038/ncomms6937
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