Drosophila deltex mediates suppressor of Hairless-independent and late-endosomal activation of Notch signaling.
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 (Dl)/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.
Hori
Kazuya
K
Department of Biological Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Fostier
Maggy
M
Ito
Mikiko
M
Fuwa
Takashi J
TJ
Go
Masahiro J
MJ
Okano
Hideyuki
H
Baron
Martin
M
Matsuno
Kenji
K
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D021381:Protein Transport; D051880:Receptors, Notch; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014921:Wings, Animal / Q000378:metabolism
C086679:DX protein, Drosophila; D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; D012097:Repressor Proteins; C088731:Su(H) protein, Drosophila