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

Iwan Evans, P Ghai, V Urbančič, Kiri L Tan, Will Wood

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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
Original languageEnglish
Pages (from-to)709-720
Number of pages12
JournalCell Death and Differentiation
Volume20
Issue number5
Early online date18 Jan 2013
DOIs
Publication statusPublished - May 2013

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Cadaver
Drosophila
Macrophages
Pseudopodia
Phagocytosis
Wounds and Injuries
Actin-Related Protein 2-3 Complex
Phagosomes
Phagocytes
Actin Cytoskeleton
Cell Movement
Embryonic Structures
Apoptosis
Pathology
Neoplasms

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SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila. / Evans, Iwan; Ghai, P; Urbančič, V; Tan, Kiri L; Wood, Will.

In: Cell Death and Differentiation, Vol. 20, No. 5, 05.2013, p. 709-720.

Research output: Contribution to journalArticle

Evans, Iwan ; Ghai, P ; Urbančič, V ; Tan, Kiri L ; Wood, Will. / SCAR/WAVE-mediated processing of engulfed apoptotic corpses is essential for effective macrophage migration in Drosophila. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 5. pp. 709-720.
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