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

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)235-241
Number of pages7
JournalJournal of biochemistry
Volume155
Issue number4
DOIs
Publication statusPublished - 2014 Apr

Keywords

  • autotoxin
  • cardia bifida
  • lysophosphatidic acid
  • sphingosine-1-phosphate
  • zebrafish

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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