title: AP-1 controls the trafficking of Notch and Sanpodo toward E-cadherin junctions in sensory organ precursors.
abstract: In Drosophila melanogaster, external sensory organs develop from a single sensory organ precursor (SOP). The SOP divides asymmetrically to generate daughter cells, whose fates are governed by differential Notch activation. Here we show that the clathrin adaptor AP-1 complex, localized at the trans Golgi network and in recycling endosomes, acts as a negative regulator of Notch signaling. Inactivation of AP-1 causes ligand-dependent activation of Notch, leading to a fate transformation within sensory organs. Loss of AP-1 affects neither cell polarity nor the unequal segregation of the cell fate determinants Numb and Neuralized. Instead, it causes apical accumulation of the Notch activator Sanpodo and stabilization of both Sanpodo and Notch at the interface between SOP daughter cells, where DE-cadherin is localized. Endocytosis-recycling assays reveal that AP-1 acts in recycling endosomes to prevent internalized Spdo from recycling toward adherens junctions. Because AP-1 does not prevent endocytosis and recycling of the Notch ligand Delta, our data indicate that the DE-cadherin junctional domain may act as a launching pad through which endocytosed Notch ligand is trafficked for signaling.
authors.affiliation: CNRS UMR 6061-Institut de Génétique et Développement de Rennes, Université de Rennes 1, 2 avenue du Professeur Bernard, 35000 Rennes, France.
authors.forename: Najate
authors.initials: N
authors.lastname: Benhra
authors.forename: Sylvie
authors.initials: S
authors.lastname: Lallet
authors.forename: Mathieu
authors.initials: M
authors.lastname: Cotton
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Bras
authors.forename: Aurore
authors.initials: A
authors.lastname: Dussert
authors.forename: Roland
authors.initials: R
authors.lastname: Le Borgne
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism*; D012679:Sense Organs / Q000196:embryology / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D015820:Cadherins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D018808:Transcription Factor AP-1; C112833:spdo protein, Drosophila