Identification of cytoskeletal regulatory proteins required for efficient phagocytosis in Drosophila

Microbes Infect. 2003 Aug;5(10):815-24. doi: 10.1016/s1286-4579(03)00157-6.

Abstract

Phagocytosis is a complex and apparently evolutionarily conserved process that plays a central role in the immune response to infection. By ultrastructural and functional criteria, Drosophila hemocyte (macrophage) phagocytosis resembles mammalian phagocytosis. Using a non-saturated forward genetic screen for larval hemocyte phagocytosis mutants, D-SCAR and profilin were identified as important regulators of phagocytosis in Drosophila. In both hemocytes ex vivo and the macrophage-like S2 cell line, lack of D-SCAR significantly decreased phagocytosis of Escherichia coli and Staphylococcus aureus. In contrast, profilin mutant hemocytes exhibited increased phagocytic activity. Analysis of double mutants suggests that D-SCAR and profilin interact during phagocytosis. Finally, RNA interference studies in S2 cells indicated that the D-SCAR homolog D-WASp also participates in phagocytosis. This study demonstrates that Drosophila provides a viable model system in which to dissect the complex interactions that regulate phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actin Cytoskeleton / genetics
  • Actin Cytoskeleton / metabolism
  • Animals
  • Contractile Proteins*
  • Cytochalasin D / pharmacology
  • Down-Regulation
  • Drosophila / immunology
  • Drosophila / physiology*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila Proteins / physiology*
  • Hemocytes / cytology
  • Hemocytes / metabolism
  • Hemocytes / physiology*
  • Hemocytes / ultrastructure
  • Microfilament Proteins / genetics
  • Microfilament Proteins / physiology
  • Mutagenesis, Insertional
  • Mutation
  • Phagocytosis / drug effects
  • Phagocytosis / genetics
  • Phagocytosis / physiology*
  • Profilins
  • Up-Regulation
  • Wiskott-Aldrich Syndrome Protein

Substances

  • Contractile Proteins
  • Drosophila Proteins
  • Microfilament Proteins
  • Profilins
  • SCAR protein, Drosophila
  • WASp protein, Drosophila
  • Wiskott-Aldrich Syndrome Protein
  • chic protein, Drosophila
  • Cytochalasin D