PI(4,5)P2 Produced by the PI4P5K SKTL Controls Apical Size by Tethering PAR-3 in Drosophila Epithelial Cells
Autor: | Julie Jouette, Kevin Legent, Antoine Guichet, Sandra B Claret, Béatrice Benoit |
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Přispěvatelé: | Institut Jacques Monod (IJM (UMR_7592)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Association pour la Recherche sur le Cancer (ARC), CNRS, ARC (grant SL220100601358), Ligue Contre le Cancer (grant RS11/75-34) |
Rok vydání: | 2014 |
Předmět: |
Phosphatase
Biology Phosphatidylinositols General Biochemistry Genetics and Molecular Biology Adherens junction Cell polarity Morphogenesis medicine Animals Drosophila Proteins [SDV.BDD]Life Sciences [q-bio]/Development Biology Cytoskeleton Epithelial polarity Agricultural and Biological Sciences(all) Biochemistry Genetics and Molecular Biology(all) Kinase Cell Membrane Actin cytoskeleton reorganization Intracellular Signaling Peptides and Proteins Cell Polarity Epithelial Cells Apical constriction Adherens Junctions Actins Epithelium Cell biology Drosophila melanogaster medicine.anatomical_structure General Agricultural and Biological Sciences |
Zdroj: | Current Biology-CB Current Biology-CB, Elsevier, 2014, 24 (10), pp.1071-9. ⟨10.1016/j.cub.2014.03.056⟩ |
ISSN: | 0960-9822 1879-0445 |
Popis: | International audience; BACKGROUND: The control of apical-basal polarity in epithelial layers is a fundamental event in many processes, ranging from embryonic development to tumor formation. A key feature of polarized epithelial cells is their ability to maintain an asymmetric distribution of specific molecular complexes, including the phosphoinositides PI(4,5)P2 and PI(3,4,5)P3. The spatiotemporal regulation of these phosphoinositides is controlled by the concerted action of phosphoinositide kinases and phosphatases. RESULTS: Using the Drosophila follicular epithelium as a model system in vivo, we show here that PI(4,5)P2 is crucial to maintain apical-basal polarity. PI(4,5)P2 is essentially regulated by the PI4P5 kinase Skittles (SKTL), whereas neither the phosphatase PTEN nor the PI(4,5)P3 kinase DP110 lead to loss of apical-basal polarity. By inactivating SKTL and thereby strongly reducing PI(4,5)P2 levels in a single cell of the epithelium, we observe the disassembly of adherens junctions, actin cytoskeleton reorganization, and apical constriction leading to delamination, a process similar to that observed during epithelial-mesenchymal transition. We provide evidence that PI(4,5)P2 controls the apical targeting of PAR-3/Bazooka to the plasma membrane and that the loss of this polarized distribution is sufficient to induce a similar cell shape change. Finally, we show that PI(4,5)P2 is excluded from the cell apex and that PAR-3 diffuses laterally just prior to the apical constriction in a context of endogenous invagination. CONCLUSIONS: All together, these results indicate that the PIP5 kinase SKTL, by controlling PI(4,5)P2 polarity, regulates PAR-3 localization and thus the size of the apical domain. |
Databáze: | OpenAIRE |
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