title: Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation.
abstract: Cell signaling mediated by the Notch receptor (N) regulates many cell-fate decisions and is partly controlled by the endocytic trafficking of N. Drosophila deltex (dx) encodes an evolutionarily conserved regulator of N signaling, an E3-ubiquitin ligase, which ubiquitinates N's intracellular domain. Although Dx was shown to function in N endocytosis in studies of dx over-expression, the roles of endogenous Dx have remained hidden. Here, we investigated N endocytosis in a dx-null Drosophila mutant and found that endogenous Dx is required for at least two steps of N trafficking: the incorporation of N into endocytic vesicles from the plasma membrane and the transport of N from early endosomes to lysosomes. In the absence of Dx functions, N was stabilized in unknown endocytic compartments, where it was probably insulated from transport to lysosomes. We also found that canonical N signaling and Dx-mediated N signaling are activated in two different endocytic compartments, before N is incorporated into multivesicular body (MVB) interluminal vesicles and after N is transported from MVBs, respectively. The endocytic compartment in which Dx-mediated N signaling is activated appears to coincide with the activity of endogenous Dx in N trafficking. These findings extend our understanding of how N's trafficking and activation are correlated.
authors.affiliation: Department of Biological Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamada
authors.forename: Takashi J
authors.initials: TJ
authors.lastname: Fuwa
authors.forename: Tomonori
authors.initials: T
authors.lastname: Ayukawa
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Tanaka
authors.forename: Akira
authors.initials: A
authors.lastname: Nakamura
authors.forename: Marian B
authors.initials: MB
authors.lastname: Wilkin
authors.forename: Martin
authors.initials: M
authors.lastname: Baron
authors.forename: Kenji
authors.initials: K
authors.lastname: Matsuno
mesh_terms: D000818:Animals; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004705:Endocytosis; D008565:Membrane Proteins / Q000378:metabolism*; D009154:Mutation; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction; D022161:Transport Vesicles / Q000378:metabolism
chemical_list: C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch