Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate

Abstract

Cyclic ADP-ribose (cADPR), a metabolite of NAD+, is known to function as a second messenger for intracellular Ca2+ mobilization in various vertebrate and invertebrate tissues. In this study, we isolated two Xenopus laevis cDNAs (frog cd38 and cd157 cDNAs) homologous to the one encoding the human cADPR-metabolizing enzyme CD38. Frog CD38 and CD157 are 298-amino acid proteins with 35.9 and 27.2 % identity to human CD38 and CD157, respectively. Transfection of expression vectors for frog CD38 and CD157 into COS-7 cells revealed that frog CD38 had NAD+ glycohydrolase, ADP-ribosyl cyclase (ARC), and cADPR hydrolase activities, and that frog CD157 had no enzymatic activity under physiological conditions. In addition, when recombinant CD38 and frog brain homogenate were electrophoresed on an SDS–polyacrylamide gel, ARC of the brain homogenate migrated to the same position in the gel as that of frog CD38, suggesting that frog CD38 is the major enzyme responsible for cADPR metabolism in amphibian cells. The frog cd38 gene consists of eight exons and is ubiquitously expressed in various tissues. These findings provide evidence for the existence of the CD38–cADPR signaling system in frog cells and suggest that the CD38–cADPR signaling system is conserved during vertebrate evolution.

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Acknowledgments

We are grateful to Brent Bell for valuable assistance in preparing the manuscript for publication and to Yuya Shichinohe for skillful technical assistance. This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan and was submitted by T. I. in partial fulfilment of the degree of Doctor of Medical Science at Tohoku University.

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Correspondence to Takayuki Ikeda.

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Ikeda, T., Takasawa, S., Noguchi, N. et al. Identification of a major enzyme for the synthesis and hydrolysis of cyclic ADP-ribose in amphibian cells and evolutional conservation of the enzyme from human to invertebrate. Mol Cell Biochem 366, 69–80 (2012). https://doi.org/10.1007/s11010-012-1284-0

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Keywords

  • ADP-ribosyl cyclase
  • CD157
  • CD38
  • Cyclic ADP-ribose hydrolase
  • Xenopus laevis