neuralized Encodes a peripheral membrane protein involved in delta signaling and endocytosis.
Activation of the Notch (N) receptor involves an intracellular proteolytic step triggered by shedding of the extracellular N domain (N-EC) upon ligand interaction. The ligand Dl has been proposed to effect this N-EC shedding by transendocytosing the latter into the signal-emitting cell. We find that Dl endocytosis and N signaling are greatly stimulated by expression of neuralized (neur). neur inactivation suppresses Dl endocytosis, while its overexpression enhances Dl endocytosis and Notch-dependent signaling. We show that neur encodes an intracellular peripheral membrane protein. Its C-terminal RING domain is necessary for Dl accumulation in endosomes, but may be dispensable for Dl signaling. The potent modulatory effect of Neur on Dl activity makes Neur a candidate for establishing signaling asymmetries within cellular equivalence groups.
Pavlopoulos
E
E
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Crete, Greece.
Pitsouli
C
C
Klueg
K M
KM
Muskavitch
M A
MA
Moschonas
N K
NK
Delidakis
C
C
D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000196:embryology / Q000502:physiology*; D004628:Embryonic Structures / Q000166:cytology / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D017930:Genes, Reporter; D047908:Intracellular Signaling Peptides and Proteins; D008025:Ligases; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017956:Photoreceptor Cells, Invertebrate / Q000166:cytology / Q000502:physiology; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases; D014921:Wings, Animal / Q000166:cytology / Q000502:physiology
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; C064045:delta protein; D044767:Ubiquitin-Protein Ligases; C071006:neur protein, Drosophila; D008025:Ligases