Premium
Microglia release ATP by exocytosis
Author(s) -
Imura Yoshio,
Morizawa Yosuke,
Komatsu Ryohei,
Shibata Keisuke,
Shinozaki Youichi,
Kasai Hirotake,
Moriishi Kohji,
Moriyama Yoshinori,
Koizumi Schuichi
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22517
Subject(s) - exocytosis , microglia , ionomycin , microbiology and biotechnology , biology , apyrase , purinergic receptor , lysosome , adenosine triphosphate , extracellular , colocalization , pannexin , connexin , biochemistry , intracellular , secretion , gap junction , immunology , inflammation , enzyme
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 Ca 2+ , 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. GLIA 2013;61:1320–1330