A novel ryanodine receptor expressed in pancreatic islets by alternative splicing from type 2 ryanodine receptor gene.
Cyclic ADP-ribose (cADPR), a potent Ca(2+) mobilizing intracellular messenger synthesized by CD38, regulates the opening of ryanodine receptors (RyRs). Increases in intracellular Ca(2+) concentrations in pancreatic islets, resulting from Ca(2+) mobilization from RyRs as well as Ca(2+) 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 [(3)H]ryanodine binding. Intracellular Ca(2+) 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.
Takasawa
Shin
S
Department of Biochemistry, Nara Medical University, Kashihara 634-8521, Japan.
Kuroki
Michio
M
Nata
Koji
K
Noguchi
Naoya
N
Ikeda
Takayuki
T
Yamauchi
Akiyo
A
Ota
Hiroyo
H
Itaya-Hironaka
Asako
A
Sakuramoto-Tsuchida
Sumiyo
S
Takahashi
Iwao
I
Yoshikawa
Takeo
T
Shimosegawa
Tooru
T
Okamoto
Hiroshi
H
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D036563:Cyclic ADP-Ribose / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D015723:Gene Library; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D011817:Rabbits; D051381:Rats; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics* / Q000378:metabolism; D014018:Tissue Distribution
D019837:Ryanodine Receptor Calcium Release Channel; D036563:Cyclic ADP-Ribose; D004247:DNA; D002118:Calcium