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Roles of Drosophila Deltex in Notch receptor endocytic trafficking and activation
Author(s) -
Yamada Kenta,
Fuwa Takashi J.,
Ayukawa Tomonori,
Tanaka Tsubasa,
Nakamura Akira,
Wilkin Marian B.,
Baron Martin,
Matsuno Kenji
Publication year - 2011
Publication title -
genes to cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.912
H-Index - 115
eISSN - 1365-2443
pISSN - 1356-9597
DOI - 10.1111/j.1365-2443.2011.01488.x
Subject(s) - biology , endocytic cycle , notch signaling pathway , microbiology and biotechnology , receptor , drosophila (subgenus) , endocytosis , genetics , signal transduction , gene
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.