SWAP70 Is a Universal GEF-like Adaptor for Tethering Actin to Phagosomes

Small GTPases. 2019 Jul;10(4):311-323. doi: 10.1080/21541248.2017.1328302. Epub 2018 Feb 9.

Abstract

We recently identified a key role for SWAP70 as the tethering factor stabilizing F-actin filaments on the surface of phagosomes in human dendritic cells by interacting both with Rho-family GTPases and the lipid phosphatidylinositol (3,4)-bisphosphate. In this study, we aimed to investigate whether this role of SWAP70 was general among immune phagocytes. Our data reveal that SWAP70 is recruited to early phagosomes of macrophages and dendritic cells from both human and mouse. The putative inhibitor of SWAP70 sanguinarine blocked phagocytosis and F-actin polymerization, supporting a key role for SWAP70 in phagocytosis as demonstrated previously with knock-down. Moreover, SWAP70 was recently shown to sequester the F-actin severing protein cofilin and we investigated this relationship in phagocytosis. Our data show an increased activation of cellular cofilin upon siRNA knockdown of SWAP70. Finally, we explored whether SWAP70 would be recruited to the immune synapse between dendritic cells and T cells required for antigen presentation, as the formation of such synapses depends on F-actin. However, we observed that SWAP70 was depleted at immune synapses and specifically was recruited to phagosomes. Our data support an essential and specific role for SWAP70 in tethering and stabilizing F-actin to the phagosomal surface in a wide range of phagocytes.

Keywords: F-actin; Rac1; cofilin; dendritic cells; immunological synapse; macrophages; phagocytosis; phosphoinositides; sanguinarine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Cytoskeleton / metabolism*
  • Animals
  • Benzophenanthridines / pharmacology
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Dendritic Cells / cytology
  • Dendritic Cells / metabolism
  • Female
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Isoquinolines / pharmacology
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mice
  • Minor Histocompatibility Antigens / metabolism*
  • Nuclear Proteins / metabolism*
  • Phagosomes / metabolism*
  • RAW 264.7 Cells
  • Synapses / metabolism

Substances

  • Benzophenanthridines
  • DNA-Binding Proteins
  • Guanine Nucleotide Exchange Factors
  • Isoquinolines
  • Minor Histocompatibility Antigens
  • Nuclear Proteins
  • SWAP70 protein, human
  • Swap70 protein, mouse
  • sanguinarine