Synthesis of the Ca -Mobilizing Messengers NAADP
ARTICLE cro Author’s Choice Synthesis of the Ca2؉-mobilizing messengers NAADP and cADPR by intracellular CD38 enzyme in the mouse heart: Role in -adrenoceptor signaling Received for publication, April 3, 2017, and in revised form, May 13, 2017 Published, Papers in Press, May 24, 2017, DOI 10.1074/jbc.M117.789347 Wee K. Lin‡, Emma L. Bolton‡, Wilian A. Cortopassi§¶, Yanwen Wangʈ, Fiona O’Brien‡, Matylda Maciejewska‡, Matthew P. Jacobson¶, Clive Garnham‡, Margarida Ruas‡, John Parrington‡, Ming Lei‡1, Rebecca Sitsapesan‡2, Antony Galione‡3, and Derek A. Terrar‡4 From the ‡Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom, the §Department of Chemistry, Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, United Kingdom, the ¶Department of Pharmaceutical Chemistry, University of California, San Francisco, California 94158, and the ʈFaculty of Biology, Medicine, and Health, University of Manchester, Manchester M13 9NT, United Kingdom Edited by Roger J. Colbran Nicotinic acid adenine dinucleotide phosphate (NAADP) and increase both Ca2؉ transients and the tendency to disturb .cyclic ADP-ribose (cADPR) are Ca2؉-mobilizing messengers heart rhythm important for modulating cardiac excitation–contraction cou- pling and pathophysiology. CD38, which belongs to the ADP- ribosyl cyclase family, catalyzes synthesis of both NAADP and ADP-ribosyl cyclases (ARCs)5 are enzymes capable of con- cADPR in vitro. However, it remains unclear whether this is the verting NAD into cyclic adenosine diphosphate ribose main enzyme for their production under physiological condi- (cADPR). In addition, some of these cyclases (for example, tions. Here we show that membrane fractions from WT but not CD38 and Aplysia cyclase), can (at least under in vitro condi- ؊/؊ CD38 mouse hearts supported NAADP and cADPR synthe- tions) also produce nicotinic acid adenine dinucleotide phos- sis.
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