Neuralized Promotes Basal to Apical Transcytosis of Delta in Epithelial Cells
| Autor: | Najate Benhra, Aurore Dussert, Roland Le Borgne, Françoise Vignaux, François Schweisguth |
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| Přispěvatelé: | Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), This work was supported in part by grants from the Re´gion Bretagne (ACOMB ‘Notasid' 2168), from the ATIP program Centre National de la Recherche Scientifique, Association pour la Recherche sur le Cancer 4905, and Fondation pour la Recherche Médicale. |
| Rok vydání: | 2010 |
| Předmět: |
Delta
MESH: Mutation MESH: Drosophila Proteins Ubiquitin-Protein Ligases Notch signaling pathway [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology MESH: Drosophila melanogaster MESH: Dogs 03 medical and health sciences Basal (phylogenetics) Dogs Precursor cell Animals Drosophila Proteins MESH: Sense Organs MESH: Animals MESH: Pupa [SDV.BDD]Life Sciences [q-bio]/Development Biology Molecular Biology 030304 developmental biology Epithelial polarity Sensory organ 0303 health sciences Receptors Notch fungi 030302 biochemistry & molecular biology Intracellular Signaling Peptides and Proteins Pupa Cell Polarity Membrane Proteins Sense Organs Epithelial Cells Articles Cell Biology MESH: Ubiquitin-Protein Ligases Endocytosis Signaling Cell biology Drosophila melanogaster Transcytosis MESH: Epithelial Cells MESH: Endocytosis Mutation MESH: Membrane Proteins MESH: Cell Polarity MESH: Receptors Notch |
| Zdroj: | Molecular Biology of the Cell Molecular Biology of the Cell, American Society for Cell Biology, 2010, 21 (12), pp.2078-86. ⟨10.1091/mbc.E09-11-0926⟩ |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | In this article, it is shown that a pool of Delta localizes at the basolateral membrane of sensory organ precursor cells of Drosophila and of polarized MDCK cells and that Delta is endocytosed in a Neuralized-dependent manner from this basolateral membrane to allow for relocalization to the apical domain where it can bind and activate Notch. Notch receptors mediate short-range signaling controlling many developmental decisions in metazoans. Activation of Notch requires the ubiquitin-dependent endocytosis of its ligand Delta. How ligand endocytosis in signal-sending cells regulates receptor activation in juxtaposed signal-receiving cells remains largely unknown. We show here that a pool of Delta localizes at the basolateral membrane of signal-sending sensory organ precursor cells in the dorsal thorax neuroepithelium of Drosophila and that Delta is endocytosed in a Neuralized-dependent manner from this basolateral membrane. This basolateral pool of Delta is segregated from Notch that accumulates apically. Using a compartimentalized antibody uptake assay, we show that murine Delta-like 1 is similarly internalized by mNeuralized2 from the basolateral membrane of polarized Madin-Darby canine kidney cells and that internalized ligands are transcytosed to the apical plasma membrane where mNotch1 accumulates. Thus, endocytosis of Delta by Neuralized relocalizes Delta from the basolateral to the apical membrane domain. We speculate that this Neuralized-dependent transcytosis regulates the signaling activity of Delta by relocalizing Delta from a membrane domain where it cannot interact with Notch to another membrane domain where it can bind and activate Notch. |
| Databáze: | OpenAIRE |
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