title: Numb regulates the balance between Notch recycling and late-endosome targeting in Drosophila neural progenitor cells.
abstract: The Notch signaling pathway plays essential roles in both animal development and human disease. Regulation of Notch receptor levels in membrane compartments has been shown to affect signaling in a variety of contexts. Here we used steady-state and pulse-labeling techniques to follow Notch receptors in sensory organ precursor cells in Drosophila. We find that the endosomal adaptor protein Numb regulates levels of Notch receptor trafficking to Rab7-labeled late endosomes but not early endosomes. Using an assay we developed that labels different pools of Notch receptors as they move through the endocytic system, we show that Numb specifically suppresses a recycled Notch receptor subpopulation and that excess Notch signaling in numb mutants requires the recycling endosome GTPase Rab11 activity. Our data therefore suggest that Numb controls the balance between Notch receptor recycling and receptor targeting to late endosomes to regulate signaling output after asymmetric cell division in Drosophila neural progenitors.
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111 Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Seth A
authors.initials: SA
authors.lastname: Johnson
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111 University of Bridgeport, Bridgeport, CT 06604.
authors.forename: Diana
authors.initials: D
authors.lastname: Zitserman
authors.affiliation: Fox Chase Cancer Center, Philadelphia, PA 19111 Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104 fabrice.roegiers@fccc.edu.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Roegiers
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism / Q000502:physiology; D007605:Juvenile Hormones / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D021381:Protein Transport; D051880:Receptors, Notch / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000090802:rab7 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins
chemical_list: D029721:Drosophila Proteins; D007605:Juvenile Hormones; D051880:Receptors, Notch; D020691:rab GTP-Binding Proteins; D000090802:rab7 GTP-Binding Proteins; C060606:numb protein, Drosophila; C000716463:rab7 GTP-binding proteins, human; C559123:Rab11 protein, Drosophila; D000099193:rab11 GTP-Binding Proteins