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

Takayuki Ikeda, Shin Takasawa, Naoya Noguchi, Koji Nata, Akiyo Yamauchi, Iwao Takahashi, Takeo Yoshikawa, Akira Sugawara, Hideto Yonekura, Hiroshi Okamoto

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cyclic ADP-ribose (cADPR), a metabolite of NAD +, is known to function as a second messenger for intracellular Ca 2+ 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.

Original languageEnglish
Pages (from-to)69-80
Number of pages12
JournalMolecular and Cellular Biochemistry
Volume366
Issue number1-2
DOIs
Publication statusPublished - 2012 Jul

Keywords

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

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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