Rab35 regulates phagosome formation through recruitment of ACAP2 in macrophages during FcγR-mediated phagocytosis

Youhei Egami, Mitsunori Fukuda, Nobukazu Araki

    Research output: Contribution to journalArticlepeer-review

    53 Citations (Scopus)

    Abstract

    Phagosome formation and subsequent maturation are complex sequences of events that involve actin cytoskeleton remodeling and membrane trafficking. Here, we demonstrate that the Ras-related protein Rab35 is involved in the early stage of FcγR-mediated phagocytosis in macrophages. Live-cell image analysis revealed that Rab35 was markedly concentrated at the membrane where IgGopsonized erythrocytes (IgG-Es) are bound. Rab35 silencing by RNA interference (RNAi) or the expression of GDP- or GTP-locked Rab35 mutant drastically reduced the rate of phagocytosis of IgG-Es. Actin-mediated pseudopod extension to form phagocytic cups was disturbed by the Rab35 silencing or the expression of GDP-Rab35, although initial actin assembly at the IgG-E binding sites was not inhibited. Furthermore, GTP-Rab35-dependent recruitment of ACAP2, an ARF6 GTPase-activating protein, was shown in the phagocytic cup formation. Concomitantly, overexpression of ACAP2 along with GTP-locked Rab35 showed a synergistic inhibitory effect on phagocytosis. It is likely that Rab35 regulates actin-dependent phagosome formation by recruiting ACAP2, which might control actin remodeling and membrane traffic through ARF6.

    Original languageEnglish
    Pages (from-to)3557-3567
    Number of pages11
    JournalJournal of cell science
    Volume124
    Issue number21
    DOIs
    Publication statusPublished - 2011 Nov 1

    Keywords

    • Acap2
    • Actin cytoskeleton
    • Live-cell imaging
    • Macrophages
    • Phagocytosis
    • Rab35

    ASJC Scopus subject areas

    • Cell Biology

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