Abstract
CYCLIC ADP-ribose (cADPR) is a newly identified nucleotide1,2 which can release calcium from a variety of cells3–6, suggesting it is a messenger for mobilizing internal Ca2+ stores. Its cyclic structure has now been confirmed by X-ray crystallography7. Available results are consistent with it being a modulator of Ca2+ -induced Ca2+ release8–10. 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 Ca2+ -induced Ca2+ release, can also mimic calmodulin in conferring cADPR-sensitivity. Although evidence indicates that cADPR may be an activator of the ryanodine receptor8–10, present results point to the importance of accessory proteins such as calmodulin in modulating its activity.
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Lee, H., Aarhus, R., Graeff, R. et al. Cyclic ADP ribose activation of the ryanodine receptor is mediated by calmodulin. Nature 370, 307–309 (1994). https://doi.org/10.1038/370307a0
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DOI: https://doi.org/10.1038/370307a0
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