title: Sperm express a Ca2+-regulated NAADP synthase.
abstract: NAADP (nicotinic acid-adenine dinucleotide phosphate), the most potent Ca2+-mobilizing second messenger, is active in a wide range of organisms and cell types. Until now, all NAADP-producing enzymes have been thought to be members of the ADP-ribosyl cyclase family. ADP-ribosyl cyclases exhibit promiscuous substrate selectivity, synthesize a variety of products and are regulated in a limited manner, which may be non-physiological. In the present paper, we report the presence of an enzyme on the surface of sea urchin sperm that exhibits bell-shaped regulation by Ca2+ over a range (EC(50) of 10 nM and IC(50) of 50 microM) that is physiologically relevant. Uniquely, this surface enzyme possesses complete selectivity for nucleotides with a 2'-phosphate group and exhibits only base-exchange activity without any detectable cyclase activity. Taken together, these findings indicate that this novel enzyme should be considered as the first true NAADP synthase.
authors.affiliation: Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK.
authors.forename: Sridhar R
authors.initials: SR
authors.lastname: Vasudevan
authors.forename: Antony
authors.initials: A
authors.lastname: Galione
authors.forename: Grant C
authors.initials: GC
authors.lastname: Churchill
mesh_terms: D036541:ADP-ribosyl Cyclase / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D008297:Male; D009249:NADP / Q000031:analogs & derivatives* / Q000096:biosynthesis; D009713:Nucleotidyltransferases / Q000378:metabolism*; D012617:Sea Urchins; D013094:Spermatozoa / Q000201:enzymology / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D009249:NADP; C024376:NAADP; C528009:NAADP synthase, Lytechinus pictus; D009713:Nucleotidyltransferases; D036541:ADP-ribosyl Cyclase; D002118:Calcium