SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila

• Published in: Cell death and differentiation Vol. 20; no. 5; pp. 709 - 720
• Main Authors: Evans, I R, Ghai, P A, Urbančič, V, Tan, K-L, Wood, W
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-05-2013; Nature Publishing Group
• Subjects: 631/250/2504/342; 631/80/82/23; 631/80/84; 631/80/86; Actin Cytoskeleton - metabolism; Actin Cytoskeleton - ultrastructure; Actin-Related Protein 2-3 Complex - metabolism; Animals; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cell Biology; Cell Cycle Analysis; Cell death; Cell division; Cell Movement; Drosophila; Drosophila - physiology; Drosophila Proteins - metabolism; Embryos; Insects; Life Sciences; Macrophages - physiology; Microfilament Proteins - metabolism; Motility; Original Paper; Pathogens; Phagocytosis; Phagosomes - metabolism; Phosphorylation; Pseudopodia - metabolism; Pseudopodia - ultrastructure; Signal Transduction; Stem Cells; United Kingdom > UK; migration; apoptosis; macrophage; hemocyte; SCAR/WAVE
• ISSN: 1350-9047; 1476-5403
• DOI: 10.1038/cdd.2012.166

In vitro
studies have shown that SCAR/WAVE activates the Arp2/3 complex to generate actin filaments, which in many cell types are organised into lamellipodia that are thought to have an important role in cell migration. Here we demonstrate that SCAR is utilised by
Drosophila
macrophages to drive their developmental and inflammatory migrations and that it is regulated via the Hem/Kette/Nap1-containing SCAR/WAVE complex. SCAR is also important in protecting against bacterial pathogens and in wound repair as
SCAR
mutant embryos succumb more readily to both sterile and infected wounds. However, in addition to driving the formation of lamellipodia in macrophages, SCAR is required cell autonomously for the correct processing of phagocytosed apoptotic corpses by these professional phagocytes. Removal of this phagocytic burden by preventing apoptosis rescues macrophage lamellipodia formation and partially restores motility. Our results show that efficient processing of phagosomes is critical for effective macrophage migration
in vivo
. These findings have important implications for the resolution of macrophages from chronic wounds and the behaviour of those associated with tumours, because phagocytosis of debris may serve to prolong the presence of these cells at these sites of pathology.