FBP17 mediates a common molecular step in the formation of podosomes and phagocytic cups in macrophages

Shigeru Tsuboi, Hidetoshi Takada, Toshiro Hara, Naoki Mochizuki, Tomihisa Funyu, Hisao Saitoh, Yuriko Terayama, Kanemitsu Yamaya, Chikara Ohyama, Shigeaki Nonoyama, Hans D. Ochs

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Abstract

Macrophages act to protect the body against inflammation and infection by engaging in chemotaxis and phagocytosis. In chemotaxis, macrophages use an actin-based membrane structure, the podosome, to migrate to inflamed tissues. In phagocytosis, macrophages form another type of actin-based membrane structure, the phagocytic cup, to ingest foreign materials such as bacteria. The formation of these membrane structures is severely affected in macrophages from patients with Wiskott-Aldrich syndrome (WAS), an X chromosome-linked immunodeficiency disorder. WAS patients lack WAS protein (WASP), suggesting that WASP is required for the formation of podosomes and phagocytic cups. Here we have demonstrated that formin-binding protein 17 (FBP17) recruits WASP, WASP-interacting protein (WIP), and dynamin-2 to the plasma membrane and that this recruitment is necessary for the formation of podosomes and phagocytic cups. The N-terminal EFC (extended FER-CIP4 homology)/F-BAR (FER-CIP4 homology and Bin-amphiphysin-Rvs) domain of FBP17 was previously shown to have membrane binding and deformation activities. Our results suggest that FBP17 facilitates membrane deformation and actin polymerization to occur simultaneously at the same membrane sites, which mediates a common molecular step in the formation of podosomes and phagocytic cups. These results provide a potential mechanism underlying the recurrent infections in WAS patients.

Original languageEnglish
Pages (from-to)8548-8556
Number of pages9
JournalJournal of Biological Chemistry
Volume284
Issue number13
DOIs
Publication statusPublished - Mar 27 2009

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Tsuboi, S., Takada, H., Hara, T., Mochizuki, N., Funyu, T., Saitoh, H., Terayama, Y., Yamaya, K., Ohyama, C., Nonoyama, S., & Ochs, H. D. (2009). FBP17 mediates a common molecular step in the formation of podosomes and phagocytic cups in macrophages. Journal of Biological Chemistry, 284(13), 8548-8556. https://doi.org/10.1074/jbc.M805638200