Nature Cell Biology
- 8, 963 - 970 (2006)
Published online: 20 August 2006; | doi:10.1038/ncb1461
There is a Corrigendum (October 2006) associated with this Letter.
Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cellsAma Gassama-Diagne1, 2, Wei Yu1, Martin ter Beest1, 7, Fernando Martin-Belmonte1, Arlinet Kierbel3, Joanne Engel3, 4 & Keith Mostov1, 51
Department of Anatomy, University of California, San Francisco, CA, 94143, USA. 2
Institut Federatif de Recherche Claude de Preval, IFR30, INSERM Unite 563, Departement Lipoproteines et Mediateurs Lipidiques, Hopital Purpan, 31059 Toulouse Cedex, France. 3
Departments of Medicine, University of California, San Francisco, CA 94143, USA. 4
Microbiology and Immunology, University of California, San Francisco, CA 94143, USA. 5
Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA. 7
Current address: The Vontz Center, University of Cincinnati College of Medicine, 3125 Eden Avenue ML0581 Cincinnati, OH 45267-0581, USA.
Correspondence should be addressed to Ama Gassama-Diagne gassama@toulouse.inserm.fr Polarity is a central feature of eukaryotic cells and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) has a central role in the polarization of neurons and chemotaxing cells. In polarized epithelial cells, PtdIns(3,4,5)P3 is stably localized at the basolateral plasma membrane, but excluded from the apical plasma membrane, as shown by localization of GFP fused to the PtdIns(3,4,5)P3-binding pleckstrin-homology domain of Akt (GFP-PH–Akt), a fusion protein that indicates the location of PtdIns(3,4,5)P3. Here, we ectopically inserted exogenous PtdIns(3,4,5)P3 into the apical plasma membrane of polarized Madin-Darby canine kidney (MDCK) cells. Within 5 min many cells formed protrusions that extended above the apical surface. These protrusions contained basolateral plasma membrane proteins and excluded apical proteins, indicating that their plasma membrane was transformed from apical to basolateral. Addition of PtdIns(3,4,5)P3 to the basolateral surface of MDCK cells grown as cysts caused basolateral protrusions. MDCK cells grown in the presence of a phosphatidylinositol 3-kinase inhibitor had abnormally short lateral surfaces, indicating that PtdIns(3,4,5)P3 regulates the formation of the basolateral surface.
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