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| Drosophila deltex mediates suppressor of hairless-independent and late-endosomal activation of Notch signaling |
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| Author(s): Hori K, Fostier M, Ito M, Fuwa TJ, Go MJ, Okano H, Baron M, Matsuno K |
| Source: DEVELOPMENT Volume: 131 Issue: 22 Pages: 5527-5537 Published: NOV 2004 |
| Times Cited: 69 References: 67 |
| Abstract: Notch (N) signaling is an evolutionarily conserved mechanism that regulates many cell-fate decisions. deltex (dx) encodes an E3-ubiquitin ligase that binds to the intracellular domain of N and positively regulates N signaling. However, the precise mechanism of Dx action is unknown. Here, we found that Dx was required and sufficient to activate the expression of gene targets of the canonical Su(H)-dependent N signaling pathway. Although Dx required N and a cis-acting element that overlaps with the Su(H)-binding site, Dx activated a target enhancer of N signaling, the dorsoventral compartment boundary enhancer of vestigial (vgBE), in a manner that was independent of the Delta (DI)/Serrate (Ser) ligands- or Su(H). Dx caused N to be moved from the apical cell surface into the late-endosome, where it accumulated stably and co-localized with Dx. Consistent with this, the dx gene was required for the presence of N in the endocytic vesicles. Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)independent N signaling. |
| Document Type: Article |
| Language: English |
| Reprint Address: Matsuno, K (reprint author), Sci Univ Tokyo, Dept Biol Sci & Technol, 2641 Yamazaki, Noda, Chiba 2788510 Japan |
Addresses:
1. Sci Univ Tokyo, Dept Biol Sci & Technol, Noda, Chiba 2788510 Japan
2. Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs England
3. Univ Tokushima, Sch Med, Dept Nutr, Tokushima 7708503, Japan
4. Kumamoto Univ, Dept Neurosci & Immunol, Grad Sch Med Sci, Kumamoto 8600811, Japan
5. Keio Univ, Sch Med, Dept Physiol, Shinjuku Ku, Tokyo 1608582, Japan
6. Sci Univ Tokyo, Genome & Drug Res Ctr, Noda, Chiba 2788510 Japan
7. JST, PRESTO, Kawaguchi, Saitama Japan |
| Publisher: COMPANY OF BIOLOGISTS LTD, BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND |
| Subject Category: Developmental Biology |
| IDS Number: 878MQ |
| ISSN: 0950-1991 |
| DOI: 10.1242/dev.01448 |
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