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Rac1 switching at the right time and location is essential for Fcγ receptor-mediated phagosome formation.

Authors
  • Ikeda, Yuka1
  • Kawai, Katsuhisa1
  • Ikawa, Akira1
  • Kawamoto, Kyoko1
  • Egami, Youhei1
  • Araki, Nobukazu2
  • 1 Department of Histology and Cell Biology, School of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan. , (Japan)
  • 2 Department of Histology and Cell Biology, School of Medicine, Kagawa University, Miki, Kagawa 761-0793, Japan [email protected] , (Japan)
Type
Published Article
Journal
Journal of Cell Science
Publisher
The Company of Biologists
Publication Date
Aug 01, 2017
Volume
130
Issue
15
Pages
2530–2540
Identifiers
DOI: 10.1242/jcs.201749
PMID: 28600322
Source
Medline
Keywords
License
Unknown

Abstract

Lamellipodia are sheet-like cell protrusions driven by actin polymerization mainly through Rac1, a GTPase molecular switch. In Fcγ receptor-mediated phagocytosis of IgG-opsonized erythrocytes (IgG-Es), Rac1 activation is required for lamellipodial extension along the surface of IgG-Es. However, the significance of Rac1 deactivation in phagosome formation is poorly understood. Our live-cell imaging and electron microscopy revealed that RAW264 macrophages expressing a constitutively active Rac1 mutant showed defects in phagocytic cup formation, while lamellipodia were formed around IgG-Es. Because activated Rac1 reduced the phosphorylation levels of myosin light chains, failure of the cup formation is probably due to inhibition of actin/myosin II contractility. Reversible photo-manipulation of the Rac1 switch in macrophages fed with IgG-Es could phenocopy two lamellipodial motilities: outward-extension and cup-constriction by Rac1 ON and OFF, respectively. In conjunction with fluorescence resonance energy transfer imaging of Rac1 activity, we provide a novel mechanistic model of phagosome formation spatiotemporally controlled by Rac1 switching within a phagocytic cup.

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