A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene

Shin Takasawa, Michio Kuroki, Koji Nata, Naoya Noguchi, Takayuki Ikeda, Akiyo Yamauchi, Hiroyo Ota, Asako Itaya-Hironaka, Sumiyo Sakuramoto-Tsuchida, Iwao Takahashi, Takeo Yoshikawa, Tooru Shimosegawa, Hiroshi Okamoto

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Cyclic ADP-ribose (cADPR), a potent Ca2+ mobilizing intracellular messenger synthesized by CD38, regulates the opening of ryanodine receptors (RyRs). Increases in intracellular Ca2+ concentrations in pancreatic islets, resulting from Ca2+ mobilization from RyRs as well as Ca2+ influx from extracellular sources, are important in insulin secretion by glucose. In the present study, by screening a rat islet cDNA library, we isolated a novel RyR cDNA (the islet-type RyR), which is generated from the RyR2 gene by alternative splicing of exons 4 and 75. When the expression vectors for the islet-type and the authentic RyRs were transfected into HEK293 cells, the islet-type RyR2 as well as the authentic one showed high affinity [3H]ryanodine binding. Intracellular Ca2+ release in the islet-type RyR2-transfected cells was enhanced in the presence of cADPR but not in the authentic RyR2-transfected cells. The islet-type RyR2 mRNA was expressed in a variety of tissues such as in pancreatic islets, cerebrum, and cerebellum, whereas the authentic RyR2 mRNA was predominantly expressed in heart and aorta. These results suggest that the islet-type RyR2 may be an intracellular target for cADPR signaling.

Original languageEnglish
Pages (from-to)140-145
Number of pages6
JournalBiochemical and biophysical research communications
Volume397
Issue number2
DOIs
Publication statusPublished - 2010 Jun 25

Keywords

  • Alternative splicing
  • Cyclic ADP-ribose
  • Pancreatic islets
  • Ryanodine receptor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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