Synaptotagmin XI regulates phagocytosis and cytokine secretion in macrophages

Guillermo Arango Duque, Mitsunori Fukuda, Albert Descoteaux

    Research output: Contribution to journalArticlepeer-review

    31 Citations (Scopus)

    Abstract

    Synaptotagmins (Syts) are a group of type I membrane proteins that regulate vesicle docking and fusion in processes such as exocytosis and phagocytosis. All Syts possess a single transmembrane domain, and two conserved tandem Ca 2+-binding C2 domains. However, Syts IV and XI possess a conserved serine in their C2A domain that precludes these Syts from binding Ca 2+ and phospholipids, and from mediating vesicle fusion. Given the importance of vesicular trafficking in macrophages, we investigated the role of Syt XI in cytokine secretion and phagocytosis. We demonstrated that Syt XI is expressed in murine macrophages, localized in recycling endosomes, lysosomes, and recruited to phagosomes. Syt XI had a direct effect on phagocytosis and on the secretion of TNF and IL-6. Whereas small interfering RNA-mediated knockdown of Syt XI potentiated secretion of these cytokines and particle uptake, overexpression of an Syt XI construct suppressed these processes. In addition, Syt XI knockdown led to decreased recruitment of gp91phox and lysosomal-associated membrane protein-1 to phagosomes, suggesting attenuated microbicidal activity. Remarkably, knockdown of Syt XI ensued in enhanced bacterial survival. Our data reveal a novel role for Syt XI as a regulator of cytokine secretion, particle uptake, and macrophage microbicidal activity.

    Original languageEnglish
    Pages (from-to)1737-1745
    Number of pages9
    JournalJournal of Immunology
    Volume190
    Issue number4
    DOIs
    Publication statusPublished - 2013 Feb 15

    ASJC Scopus subject areas

    • Immunology and Allergy
    • Immunology

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