title: Interaction between Notch and Hif-alpha in development and survival of Drosophila blood cells.
abstract: A blood cell type termed crystal cell in Drosophila functions in clotting and wound healing and requires Notch for specification and maintenance. We report that crystal cells express elevated levels of Sima protein orthologous to mammalian hypoxia-inducible factor-α (Hif-α) even under conditions of normal oxygen availability. In these platelet-like crystal cells, Sima activates full-length Notch receptor signaling via a noncanonical, ligand-independent mechanism that promotes hemocyte survival during both normal hematopoietic development and hypoxic stress. This interaction initiates in early endosomes, is independent of Hif-β (Τangο in Drosophila), and does not activate hypoxia response targets. Studies in vertebrate myeloid cells have shown a similar up-regulation of Hif-α protein in well-oxygenated environments. This study provides a mechanistic paradigm for Hif-α/Notch interaction that may be conserved in mammals.
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Tina
authors.initials: T
authors.lastname: Mukherjee
authors.forename: William Sang
authors.initials: WS
authors.lastname: Kim
authors.forename: Lolitika
authors.initials: L
authors.lastname: Mandal
authors.forename: Utpal
authors.initials: U
authors.lastname: Banerjee
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D015687:Cell Hypoxia; D002470:Cell Survival; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004705:Endocytosis; D006410:Hematopoiesis; D006434:Hemocytes / Q000166:cytology* / Q000502:physiology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D051880:Receptors, Notch / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013312:Stress, Physiological
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; C100429:Sima protein, Drosophila; C109766:tgo protein, Drosophila; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator