Identification of cytoskeletal regulatory proteins required for efficient phagocytosis in Drosophila.
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.
Pearson
Alan M
AM
Department of Pediatrics, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Baksa
Katalin
K
Rämet
Mika
M
Protas
Meredith
M
McKee
Mary
M
Brown
Dennis
D
Ezekowitz
R Alan B
RA
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003285:Contractile Proteins; D015638:Cytochalasin D / Q000494:pharmacology; D015536:Down-Regulation; D004330:Drosophila / Q000276:immunology / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006434:Hemocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D008840:Microfilament Proteins / Q000235:genetics / Q000502:physiology; D016254:Mutagenesis, Insertional; D009154:Mutation; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051304:Profilins; D015854:Up-Regulation; D051316:Wiskott-Aldrich Syndrome Protein
D003285:Contractile Proteins; D029721:Drosophila Proteins; D008840:Microfilament Proteins; D051304:Profilins; C449671:SCAR protein, Drosophila; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C495737:chic protein, Drosophila; D015638:Cytochalasin D