Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity

Keiko Ohsawa, Yoshinori Imai, Yo Sasaki, Shinichi Kohsaka

Research output: Contribution to journalArticle

144 Scopus citations

Abstract

Ionized calcium binding adaptor molecule 1 (Iba1) is a microglia/macrophage-specific calcium-binding protein. Iba1 has the actin-bundling activity and participates in membrane ruffling and phagocytosis in activated microglia. In order to understand the Iba1-related intracellular signalling pathway in greater detail, we employed a yeast two-hybrid screen to isolate an Iba1-interacting molecule and identified another actin-bundling protein, L-fimbrin. In response to stimulation, L-fimbrin accumulated and co-localized with Iba1 in membrane ruffles induced by M-CSF-stimulation and phagocytic cups formed by IgG-opsonized beads in microglial cell line MG5. L-fimbrin was shown to associate with Iba1 in cell lysate of COS-7 expressing L-fimbrin and Iba1. By using purified proteins, direct binding of Iba1 to L-fimbrin was demonstrated by immunoprecipitation, glutathione S-transferase pull-down assays and ligand overlay assays. The binding of Iba1 was also found to increase the actin-bundling activity of L-fimbrin. These results indicate that Iba1 forms complexes with L-fimbrin in membrane ruffles and phagocytic cups, and suggest that Iba1 co-operates with L-fimbrin in modulating actin reorganization to facilitate cell migration and phagocytosis by microglia.

Original languageEnglish
Pages (from-to)844-856
Number of pages13
JournalJournal of Neurochemistry
Volume88
Issue number4
DOIs
StatePublished - Feb 2004
Externally publishedYes

Keywords

  • Actin
  • Fimbrin
  • Ionized calcium binding adaptor molecule 1
  • Membrane ruffling
  • Phagocytosis
  • Rac

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