neuralized Encodes a peripheral membrane protein involved in delta signaling and endocytosis. |
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Authors: | E Pavlopoulos C Pitsouli K M Klueg M A Muskavitch N K Moschonas C Delidakis |
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Institution: | Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, Crete, Greece. |
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Abstract: | 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. |
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