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.
Lee
H C
HC
Department of Physiology, University of Minnesota, Minneapolis 55455.
Aarhus
R
R
Graeff
R
R
Gurnack
M E
ME
Walseth
T F
TF
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