Endocytic pathway is required for Drosophila Toll innate immune signaling

Proc Natl Acad Sci U S A. 2010 May 4;107(18):8322-7. doi: 10.1073/pnas.1004031107. Epub 2010 Apr 19.

Abstract

The Toll signaling pathway is required for the innate immune response against fungi and Gram-positive bacteria in Drosophila. Here we show that the endosomal proteins Myopic (Mop) and Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) are required for the activation of the Toll signaling pathway. This requirement is observed in cultured cells and in flies, and epistasis experiments show that the Mop protein functions upstream of the MyD88 adaptor and the Pelle kinase. Mop and Hrs, which are critical components of the ESCRT-0 endocytosis complex, colocalize with the Toll receptor in endosomes. We conclude that endocytosis is required for the activation of the Toll signaling pathway.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Drosophila Proteins / genetics
  • Drosophila Proteins / immunology*
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / metabolism
  • Endocytosis*
  • Endosomal Sorting Complexes Required for Transport / genetics
  • Endosomal Sorting Complexes Required for Transport / immunology*
  • Immunity, Innate*
  • Phosphoproteins / genetics
  • Phosphoproteins / immunology*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases / immunology*
  • RNA Interference
  • Signal Transduction*
  • Toll-Like Receptors / immunology*
  • Toll-Like Receptors / metabolism

Substances

  • Drosophila Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Phosphoproteins
  • Toll-Like Receptors
  • hepatocyte growth factor-regulated tyrosine kinase substrate
  • Mop protein, Drosophila
  • Protein Tyrosine Phosphatases