RRC ID 11720
Author Yamada K, Fuwa TJ, Ayukawa T, Tanaka T, Nakamura A, Wilkin MB, Baron M, Matsuno K.
Title Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation.
Journal Genes Cells
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.
Volume 16(3)
Pages 261-72
Published 2011-3-1
DOI 10.1111/j.1365-2443.2011.01488.x
PMID 21299753
MeSH Animals Drosophila / metabolism* Drosophila Proteins / metabolism* Endocytosis* Membrane Proteins / metabolism* Mutation Receptors, Notch / metabolism* Signal Transduction Transport Vesicles / metabolism
IF 1.922
Times Cited 34
Drosophila Oregon R (Kyorin-Fly Kyorin University Tokyo Japan) Oregon RS (Drosophila Genetic Resource Center Kyoto Institute of Technology Kyoto Japan)