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 language | English |
|---|---|
| Pages (from-to) | 1320-1330 |
| Number of pages | 11 |
| Journal | GLIA |
| Volume | 61 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2013 |
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Keywords
- ATP
- Exocytosis
- Microglia
- VNUT
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience
- Neurology
Cite this
Microglia release ATP by exocytosis. / Imura, Yoshio; Morizawa, Yosuke; Komatsu, Ryohei; Shibata, Keisuke; Shinozaki, Youichi; Kasai, Hirotake; Moriishi, Kohji; Moriyama, Yoshinori; Koizumi, Schuichi.
In: GLIA, Vol. 61, No. 8, 08.2013, p. 1320-1330.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Microglia release ATP by exocytosis
AU - Imura, Yoshio
AU - Morizawa, Yosuke
AU - Komatsu, Ryohei
AU - Shibata, Keisuke
AU - Shinozaki, Youichi
AU - Kasai, Hirotake
AU - Moriishi, Kohji
AU - Moriyama, Yoshinori
AU - Koizumi, Schuichi
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - ATP
KW - Exocytosis
KW - Microglia
KW - VNUT
UR - http://www.scopus.com/inward/record.url?scp=84880699775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84880699775&partnerID=8YFLogxK
U2 - 10.1002/glia.22517
DO - 10.1002/glia.22517
M3 - Article
VL - 61
SP - 1320
EP - 1330
JO - GLIA
JF - GLIA
SN - 0894-1491
IS - 8
ER -