Mouse SPNS2 Functions as a Sphingosine-1-Phosphate Transporter in Vascular Endothelial Cells

We show that SPNS2 functions as an S1P transporter in vascular endothelial cells but not in erythrocytes and platelets

Yu Hisano; Naoki Kobayashi; Akihito Yamaguchi; Tsuyoshi Nishi


Scholarcy highlights

  • Sphingosine-1-phosphate, a bioactive sphingolipid that is recognized by five G protein-coupled receptors and plays a key role in angiogenesis, bone homeostasis and the immune system
  • When hSPNS2 or mSPNS2 were expressed in Chinese hamster ovary cells expressing sphingosine kinase 1, the protein localized to the plasma membrane and exported S1P in a manner similar to zebrafish Spns2
  • SPNS2-deficient mice were born in the expected Mendelian ratios, they displayed an eye-open at birth phenotype, and approximately 40% of them succumbed to cryptogenic death at 4 to 5 weeks of age
  • There is no significant difference in enzymatic properties between zebrafish Spns2 and mammalian SPNS2, yolk syncytial layer is a fish-specific tissue where zebrafish Spns2 has a physiological function and supplies S1P for the regulation of myocardial precursor migration
  • Consistent with previous reports indicating a predominant role of erythrocytes in maintaining the plasma S1P level, SPNS2-deficient mice retain 60% of plasma S1P, which is likely supplied by unidentified S1P transporter(s) in erythrocytes
  • In various organs, the S1P level showed no significant differences between wild-type and SPNS2-deficient mice
  • We believe that the decrease in plasma S1P level and circulating lymphocytes in SPNS2-deficient mice might be caused by the dysfunction of SPNS2 in vascular ECs, the mice used in this study were not vascular endothelial cellspecific knock-out mice
  • S1P signaling is essential for the migration of various cell types such as lymphocytes, preosteoclasts and endothelial cells. These results, along with our previous observations that zebrafish Spns2 mutants are defective in myocardial precursor migration , indicate that SPNS2 is a common regulator of the migration of cells expressing S1P receptor

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