SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila
Open Access
- 18 January 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 20 (5), 709-720
- https://doi.org/10.1038/cdd.2012.166
Abstract
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.Keywords
This publication has 59 references indexed in Scilit:
- SCAR knockouts in Dictyostelium: WASP assumes SCAR’s position and upstream regulators in pseudopodsThe Journal of cell biology, 2012
- The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migrationThe Journal of cell biology, 2012
- Actin polymerization driven by WASH causes V-ATPase retrieval and vesicle neutralization before exocytosisThe Journal of cell biology, 2011
- RhoL controls invasion and Rap1 localization during immune cell transmigration in DrosophilaNature, 2010
- Clasp-mediated microtubule bundling regulates persistent motility and contact repulsion in Drosophila macrophages in vivoThe Journal of cell biology, 2010
- A nucleator arms race: cellular control of actin assemblyNature Reviews Molecular Cell Biology, 2010
- The SCAR and WASp nucleation‐promoting factors act sequentially to mediate Drosophila myoblast fusionEMBO Reports, 2009
- Phagosome maturation: going through the acid testNature Reviews Molecular Cell Biology, 2008
- Distinct mechanisms regulate hemocyte chemotaxis during development and wound healing in Drosophila melanogaster The Journal of cell biology, 2006
- Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.JCI Insight, 1998