Vesicular nucleotide transporter mediates ATP release and migration in neutrophils

Yuika Harada, Yuri Kato, Takaaki Miyaji, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa

研究成果: Contribution to journalArticle査読

17 被引用数 (Scopus)


Neutrophils migrate to sites infected by pathogenic microorganisms. This migration is regulated by neutrophil-secreted ATP, which stimulates neutrophils in an autocrine manner through purinergic receptors on the plasma membrane. Although previous studies have shown that ATP is released through channels at the plasma membrane of the neutrophil, it remains unknown whether it is also released through alternate secretory systems involving vesicular mechanisms. In this study, we investigated the possible involvement of vesicular nucleotide transporter (VNUT), a key molecule for vesicular storage and nucleotide release, in ATP secretion from neutrophils. RT-PCR and Western blotting analysis indicated that VNUT is expressed in mouse neutrophils. Immunohistochemical analysis indicated that VNUT mainly colocalized with matrix metalloproteinase-9 (MMP-9), a marker of tertiary granules, which are secretory organelles. In mouse neutrophils, ATP release was inhibited by clodronate, which is a potent VNUT inhibitor. Furthermore, neutrophils from VNUT/ mice did not release ATP and exhibited significantly reduced migration in vitro and in vivo. These findings suggest that tertiary granule-localized VNUT is responsible for vesicular ATP release and subsequent neutrophil migration. Thus, these findings suggest an additional mechanism through which ATP is released by neutrophils.

ジャーナルJournal of Biological Chemistry
出版ステータス出版済み - 3 9 2018

All Science Journal Classification (ASJC) codes

  • 生化学
  • 分子生物学
  • 細胞生物学


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