Cyclic ADP ribose activation of the ryanodine receptor is mediated by calmodulin.
Cyclic ADP-ribose (cADPR) is a newly identified nucleotide which can release calcium from a variety of cells, suggesting it is a messenger for mobilizing internal Ca2+ stores. Its cyclic structure has now been confirmed by X-ray crystallography. Available results are consistent with it being a modulator of Ca(2+)-induced Ca2+ release. Here we report that sea urchin egg microsomes purified by Percoll gradients lose sensitivity to cADPR, but the response can be restored by a soluble protein in the supernatant. Purification and characterization of the protein indicate that it is calmodulin. It appears to be sensitizing the Ca2+ release mechanism because caffeine and strontium, agonists of Ca(2+)-induced Ca2+ release, can also mimic calmodulin in conferring cADPR-sensitivity. Although evidence indicates that cADPR may be an activator of the ryanodine receptor, present results point to the importance of accessory proteins such as calmodulin in modulating its activity.
Department of Physiology, University of Minnesota, Minneapolis 55455.
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HC
Lee
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R
Aarhus
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R
Graeff
M E
ME
Gurnack
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TF
Walseth
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002147:Calmodulin / Q000378:metabolism*; D036563:Cyclic ADP-Ribose; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008861:Microsomes / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D010063:Ovum / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012617:Sea Urchins; D013449:Sulfonamides / Q000494:pharmacology
D015220:Calcium Channels; D002147:Calmodulin; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D013449:Sulfonamides; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; C017967:W 7; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium