Editors' ChoiceCalcium signaling

Calcium signaling: Nuclear Reaction Makes Cyclic ADP Ribose

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Science's STKE  19 Oct 1999:
Vol. 1999, Issue 4, pp. tw3
DOI: 10.1126/stke.1999.4.tw3

Ryanodine receptors, which function as calcium channels activated by binding of cyclic ADP ribose (cADPr), are present in nuclear membranes with their ligand binding sites facing the nucleoplasm. However, it has not been clear whether cADPr produced in the cytoplasm can cross nuclear membranes to reach such binding sites. Adebanjo et al. now report that ADP-ribose cyclase or CD38, the membrane-associated enzyme that generates cADPr from nicotinamide adenine dinucleotide (NAD+), is present in the inner nuclear membrane, with its catalytic region on the nucloplasmic side. In isolated nuclei from mammalian MC3T3.E1 cells treated to allow storage of calcium in the nuclear envelope, NAD+ or cADPr caused increases in the concentration of nucleoplasmic calcium. The authors propose that cADPR generated in the nucleoplasm may cause transport of calcium across the inner nuclear membrane through ryanodine receptors and could thereby influence gene expression.

Adebanjo, O.A., Anandatheerthavarada, H.K., Koval, A.P., Moonga, B.S., Biswas, G., Sun, L., Sodam, B.R., Bevis, P.J.R., Huang, C.L.-H., Epstein, S., Lai, F.A., Avadhani, N.G., and Zaidi, M. (1999) A new function for CD38/ADP-ribosyl cyclase in nuclear calcium homeostasis. Nature Cell Biol. 1: 409-414. [Online Journal]