Microglia release ATP by exocytosis

Yoshio Imura, Yosuke Morizawa, Ryohei Komatsu, Keisuke Shibata, Youichi Shinozaki, Hirotake Kasai, Kohji Moriishi, Yoshinori Moriyama, Schuichi Koizumi

    Research output: Contribution to journalArticlepeer-review

    100 Citations (Scopus)

    Abstract

    Microglia survey the brain environment by sensing several types of diffusible molecules, among which extracellular nucleotides released/leaked from damaged cells have central roles. Microglia sense ATP or other nucleotides by multiple P2 receptors, after which they change into several different phenotypes. However, so far, it is largely unknown whether microglia themselves release ATP and, if so, by what mechanism. Here we show that exocytosis is the mechanism by which microglia release ATP. When we stimulated microglia with ionomycin, they released ATP and the release was dependent on Ca2+, vesicular H+-ATPase, or SNAREs but independent of connexin/pannexin hemichannels. VNUT was found to be expressed in microglia and exhibited no colocalization with lysosome. We also visualized the exocytosis of ATP by a quinacrine-based fluorescent time-lapse imaging. Moreover, we found that lipopolysaccharide increased the ionomycin-induced release of ATP, which was dependent on the increase in VNUT. Taken together, our data suggested that exocytosis is the mechanism of ATP release from microglia. When activated, they would release ATP by increasing VNUT-dependent exocytotic mechanisms.

    Original languageEnglish
    Pages (from-to)1320-1330
    Number of pages11
    JournalGlia
    Volume61
    Issue number8
    DOIs
    Publication statusPublished - 2013 Aug

    Keywords

    • ATP
    • Exocytosis
    • Microglia
    • VNUT

    ASJC Scopus subject areas

    • Neurology
    • Cellular and Molecular Neuroscience

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