title: Numb localizes at endosomes and controls the endosomal sorting of notch after asymmetric division in Drosophila.
abstract: Numb acts as a cell-fate determinant during asymmetric and stem cell divisions in both vertebrates and invertebrates [1, 2]. In Drosophila, Numb is unequally segregated in asymmetrically dividing sensory organ precursor cells (SOPs). Numb is inherited by the pIIb cell (Notch OFF) and is absent from the pIIa cell (Notch ON) [3, 4]. Numb is required to establish directional Notch signaling during cytokinesis [3, 5-7]. Using real-time imaging of a functional GFP-tagged Numb, we show that Numb relocalizes during cytokinesis from the basal cortex of pIIb to subapical endosomes. This relocalization appeared to depend on its interaction with the α-adaptin [8, 9]. Live imaging of Sanpodo (Spdo), a membrane protein interacting with Numb and regulating the trafficking of Notch [6, 7, 10-15], revealed that Spdo is internalized during cytokinesis and coaccumulates with Numb in pIIb endosomes. Using a GFP-tagged Notch [6], we found that Notch coaccumulates with Spdo in a Numb-dependent manner in these pIIb endosomes. Numb was, however, dispensable for the internalization of Notch and Spdo. We propose that Numb interacts with internalized Spdo-Notch oligomers at sorting endosomes and inhibits the recycling of Notch, thereby creating an asymmetry in Notch distribution along the pIIa-pIIb interface and regulating binary fate choice.
authors.affiliation: Developmental and Stem Cell Biology Department, Institut Pasteur, 75015 Paris, France.
authors.forename: Lydie
authors.initials: L
authors.lastname: Couturier
authors.forename: Khallil
authors.initials: K
authors.lastname: Mazouni
authors.forename: François
authors.initials: F
authors.lastname: Schweisguth
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060049:Asymmetric Cell Division / Q000502:physiology*; D022202:Chromosomes, Artificial, Bacterial; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D007605:Juvenile Hormones / Q000235:genetics / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D008969:Molecular Sequence Data; D058953:Neural Stem Cells / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051880:Receptors, Notch / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D007605:Juvenile Hormones; C497759:N protein, Drosophila; D051880:Receptors, Notch; C060606:numb protein, Drosophila