Kenta Yamada, Takashi J Fuwa, Tomonori Ayukawa, Tsubasa Tanaka, Akira Nakamura, Marian B Wilkin, Martin Baron, Kenji Matsuno
Department of Biological Science and Technology, Tokyo University of Science, Noda, Chiba 278-8510, Japan.
Genes to cells : devoted to molecular & cellular mechanisms 2011 MarCell 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. © 2011 The Authors. Journal compilation © 2011 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.
Kenta Yamada, Takashi J Fuwa, Tomonori Ayukawa, Tsubasa Tanaka, Akira Nakamura, Marian B Wilkin, Martin Baron, Kenji Matsuno. Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation. Genes to cells : devoted to molecular & cellular mechanisms. 2011 Mar;16(3):261-72
PMID: 21299753
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