Overexpression of autotaxin, a lysophosphatidic acid-producing enzyme, enhances cardia bifida induced by hypo-sphingosine-1-phosphate signaling in zebrafish embryo

Keita Nakanaga, Kotaro Hama, Kuniyuki Kano, Takanao Sato, Hiroshi Yukiura, Asuka Inoue, Daisuke Saigusa, Hidetoshi Tokuyama, Yoshihisa Tomioka, Hiroshi Nishina, Atsuo Kawahara, Junken Aoki

研究成果: Article査読

9 被引用数 (Scopus)

抄録

Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) are second-generation lysophospholipid mediators that exert multiple biological functions through their own cognate receptors. They are both present in the blood stream, activate receptors with similar structures (endothelial differentiation gene receptors), have similar roles in the vasculature and are vasoactive. However, it is unclear whether these lysophospholipid mediators cross-talk downstream of each receptor. Here, we provide in vivo evidence that LPA signaling counteracted S1P signaling. When autotaxin (Atx), an LPA-producing enzyme, was overexpressed in zebrafish embryos by injecting atx mRNA, the embryos showed cardia bifida, a phenotype induced by down-regulation of S1P signaling. A similar cardiac phenotype was not induced when catalytically inactive Atx was introduced. The cardiac phenotype was synergistically enhanced when antisense morpholino oligonucleotides (MO) against S1P receptor (s1pr2/mil) or S1P transporter (spns2) was introduced together with atx mRNA. The Atx-induced cardia bifida was prominently suppressed when embryos were treated with an lpar1 receptor antagonist, Ki16425, or with MO against lpar1. These results provide the first in vivo evidence of cross-talk between LPA and S1P signaling.

本文言語English
ページ(範囲)235-241
ページ数7
ジャーナルJournal of biochemistry
155
4
DOI
出版ステータスPublished - 2014 4

ASJC Scopus subject areas

  • 生化学
  • 分子生物学

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