TY - JOUR
T1 - A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene
AU - Takasawa, Shin
AU - Kuroki, Michio
AU - Nata, Koji
AU - Noguchi, Naoya
AU - Ikeda, Takayuki
AU - Yamauchi, Akiyo
AU - Ota, Hiroyo
AU - Itaya-Hironaka, Asako
AU - Sakuramoto-Tsuchida, Sumiyo
AU - Takahashi, Iwao
AU - Yoshikawa, Takeo
AU - Shimosegawa, Tooru
AU - Okamoto, Hiroshi
N1 - Funding Information:
We are grateful to Mr. Brent Bell for critical reading of the manuscript. 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 is in partial fulfillment by M. K. of the degree of Doctor of Medical Science at Tohoku University.
PY - 2010/6/25
Y1 - 2010/6/25
N2 - 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.
AB - 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.
KW - Alternative splicing
KW - Cyclic ADP-ribose
KW - Pancreatic islets
KW - Ryanodine receptor
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U2 - 10.1016/j.bbrc.2010.05.051
DO - 10.1016/j.bbrc.2010.05.051
M3 - Article
C2 - 20471962
AN - SCOPUS:77955493661
SN - 0006-291X
VL - 397
SP - 140
EP - 145
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -