Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation.

Abstract

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.

DOI: 10.1111/j.1365-2443.2011.01488.x

Cite this paper

@article{Yamada2011RolesOD, title={Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation.}, author={Kenta Yamada and Takashi J Fuwa and Tomonori Ayukawa and Tsubasa Tanaka and Akira Nakamura and Marian B Wilkin and Martin Baron and Kenji Matsuno}, journal={Genes to cells : devoted to molecular & cellular mechanisms}, year={2011}, volume={16 3}, pages={261-72} }