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Published Online December 11, 2008
Science DOI: 10.1126/science.1167449

Reports

Submitted on October 20, 2008
Accepted on December 3, 2008

The Sphingolipid Transporter Spns2 Functions in Migration of Zebrafish Myocardial Precursors

Atsuo Kawahara 1*, Tsuyoshi Nishi 2, Yu Hisano 2, Hajime Fukui 3, Akihito Yamaguchi 2, Naoki Mochizuki 3

1 Department of Structural Analysis, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.; HMRO, Kyoto University Faculty of Medicine, Yoshida, Sakyo-Ku, Kyoto 606-8501, Japan.
2 Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki-shi, Osaka 567-0047, Japan.; Graduate School of Pharmaceutical Sciences, Osaka University, Suita-shi, Osaka 565-0871, Japan.
3 Department of Structural Analysis, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan.

* To whom correspondence should be addressed.
Atsuo Kawahara , E-mail: atsuo{at}ri.ncvc.go.jp

Sphingosine-1-phosphate (S1P) is a secreted lipid mediator that functions in vascular development: however, it remains unclear how S1P secretion is regulated during embryogenesis. We identified a zebrafish mutant ko157, which displays cardia bifida (two hearts) resembling the S1P receptor-2 mutant. A migration defect of myocardial precursors in the ko157 mutant is due to a mutation in a multipass transmembrane protein Spns2 and can be rescued by S1P injection. We show that the export of S1P from cells requires Spns2. spns2 is expressed in the extra-embryonic tissue yolk syncytial layer (YSL) and introduction of spns2 mRNA in the YSL restored the cardiac defect in the ko157 mutant. Thus, Spns2 in the YSL functions as a S1P transporter in S1P secretion, thereby regulating myocardial precursor migration.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Characterization of the ATP-dependent Sphingosine 1-Phosphate Transporter in Rat Erythrocytes.
N. Kobayashi, N. Kobayashi, A. Yamaguchi, and T. Nishi (2009)
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