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

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• 作者：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
• 关键词：Cyclic ADP-ribose ; Ryanodine receptor ; Alternative splicing ; Pancreatic islets
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2010
• 出版时间：25 June 2010
• 年：2010
• 卷：397
• 期：2
• 页码：140-145
• 全文大小：857 K

文摘

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.