Calmodulin is a selective mediator of Ca(2+)-induced Ca2+ release via the ryanodine receptor-like Ca2+ channel triggered by cyclic ADP-ribose.
The ryanodine receptor-like Ca2+ channel (RyRLC) is responsible for Ca2+ wave propagation and Ca2+ oscillations in certain nonmuscle cells by a Ca(2+)-induced Ca2+ release (CICR) mechanism. Cyclic ADP-ribose (cADPR), an enzymatic product derived from NAD+, is the only known endogenous metabolite that acts as an agonist on the RyRLC. However, the mode of action of cADPR is not clear. We have identified calmodulin as a functional mediator of cADPR-triggered CICR through the RyRLC in sea urchin eggs. cADPR-induced Ca2+ release consisted of two phases, an initial rapid release phase and a subsequent slower release. The second phase was selectively potentiated by calmodulin which, in turn, was activated by Ca2+ released during the initial phase. Caffeine enhanced the action of calmodulin. Calmodulin did not play a role in inositol 1,4,5-trisphosphate-induced Ca2+ release. These findings offer insights into the multiple pathways that regulate intracellular Ca2+ signaling.
Tanaka
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Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Harvard Medical School, Boston, MA 02115, USA.
Tashjian
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AH
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D036563:Cyclic ADP-Ribose; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008954:Models, Biological; D009124:Muscle Proteins / Q000187:drug effects*; D010063:Ovum / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel; D012617:Sea Urchins; D013347:Subcellular Fractions / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D002147:Calmodulin; D009124:Muscle Proteins; D019837:Ryanodine Receptor Calcium Release Channel; D013449:Sulfonamides; D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D002110:Caffeine; C017967:W 7; C034700:N-(6-aminohexyl)-1-naphthalenesulfonamide; D002118:Calcium