Roles of Drosophila deltex in Notch receptor endocytic trafficking and activation

Genes Cells. 2011 Mar;16(3):261-72. doi: 10.1111/j.1365-2443.2011.01488.x. Epub 2011 Feb 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila / metabolism*
  • Drosophila Proteins / metabolism*
  • Endocytosis*
  • Membrane Proteins / metabolism*
  • Mutation
  • Receptors, Notch / metabolism*
  • Signal Transduction
  • Transport Vesicles / metabolism


  • DX protein, Drosophila
  • Drosophila Proteins
  • Membrane Proteins
  • N protein, Drosophila
  • Receptors, Notch