SWAP70 Organizes the Actin Cytoskeleton and Is Essential for Phagocytosis.
Actin plays a critical role during the early stages of pathogenic microbe internalization by immune cells. In this study, we identified a key mechanism of actin filament tethering and stabilization to the surface of phagosomes in human dendritic cells. We found that the actin-binding protein SWAP70 is specifically recruited to nascent phagosomes by binding to the lipid phosphatidylinositol (3,4)-bisphosphate. Multi-color super-resolution stimulated emission depletion (STED) microscopy revealed that the actin cage surrounding early phagosomes is formed by multiple concentric rings containing SWAP70. SWAP70 colocalized with and stimulated activation of RAC1, a known activator of actin polymerization, on phagosomes. Genetic ablation of SWAP70 impaired actin polymerization around phagosomes and resulted in a phagocytic defect. These data show a key role for SWAP70 as a scaffold for tethering the peripheral actin cage to phagosomes.
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 28, 6525GA Nijmegen, the Netherlands.
Maksim V
MV
Baranov
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 28, 6525GA Nijmegen, the Netherlands.
Natalia H
NH
Revelo
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 28, 6525GA Nijmegen, the Netherlands.
Ilse
I
Dingjan
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Riccardo
R
Maraspini
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 28, 6525GA Nijmegen, the Netherlands.
Martin
M
Ter Beest
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, 01307 Dresden, Germany.
Alf
A
Honigmann
Department of Tumor Immunology, Radboud University Medical Center, Radboud Institute for Molecular Life Sciences, Geert Grooteplein 28, 6525GA Nijmegen, the Netherlands. Electronic address: geert.vandenbogaart@radboudUMC.nl.
Geert
G
van den Bogaart
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D010587:Phagocytosis; D010588:Phagosomes / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D058105:Polymerization; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D018129:Phosphatidylinositol Phosphates; C491873:SWAP70 protein, human; C060980:phosphatidylinositol 3,4-diphosphate; D020830:rac1 GTP-Binding Protein
Rac1; STED microscopy; SWAP70; actin; cytoskeleton; dendritic cell; phagocytosis; phosphatidylionositol 3,4-bisphosphate; phosphoinositides; rho-GTPases