title: NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms.
abstract: Nicotinamide adenine dinucleotide phosphate (NADP) is a critical cofactor during metabolism, calcium signaling, and oxidative defense, yet how animals regulate their NADP pools in vivo and how NADP-synthesizing enzymes are regulated have long remained unknown. Here we show that expression of Nadk, an NAD(+) kinase-encoding gene, governs NADP biosynthesis in vivo and is essential for development in Xenopus frog embryos. Unexpectedly, we found that embryonic Nadk expression is dynamic, showing cell type-specific up-regulation during both frog and sea urchin embryogenesis. We analyzed the NAD kinases (NADKs) of a variety of deuterostome animals, finding two conserved internal domains forming a catalytic core but a highly divergent N terminus. One type of N terminus (found in basal species such as the sea urchin) mediates direct catalytic activation of NADK by Ca(2+)/calmodulin (CaM), whereas the other (typical for vertebrates) is phosphorylated by a CaM kinase-dependent mechanism. This work indicates that animal NADKs govern NADP biosynthesis in vivo and are regulated by evolutionarily divergent and conserved CaM-dependent mechanisms.
authors.affiliation: Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway; Faculty of Life Sciences and The Healing Foundation Centre, University of Manchester, Manchester M13 9PT, United Kingdom; and.
authors.forename: Nick R
authors.initials: NR
authors.lastname: Love
authors.affiliation: Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway;
authors.forename: Nadine
authors.initials: N
authors.lastname: Pollak
authors.affiliation: Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway;
authors.forename: Christian
authors.initials: C
authors.lastname: Dölle
authors.affiliation: Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway;
authors.forename: Marc
authors.initials: M
authors.lastname: Niere
authors.affiliation: Faculty of Life Sciences and The Healing Foundation Centre, University of Manchester, Manchester M13 9PT, United Kingdom; and.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Departments of Genetics, Evolution and Environment and.
authors.forename: Paola
authors.initials: P
authors.lastname: Oliveri
authors.affiliation: Faculty of Life Sciences and The Healing Foundation Centre, University of Manchester, Manchester M13 9PT, United Kingdom; and.
authors.forename: Enrique
authors.initials: E
authors.lastname: Amaya
authors.affiliation: Cell and Developmental Biology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Sandip
authors.initials: S
authors.lastname: Patel
authors.affiliation: Department of Molecular Biology, University of Bergen, 5020 Bergen, Norway; mathias.ziegler@mbi.uib.no.
authors.forename: Mathias
authors.initials: M
authors.lastname: Ziegler
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002147:Calmodulin / Q000378:metabolism*; D017931:DNA Primers; D006367:HeLa Cells; D006801:Humans; D017403:In Situ Hybridization; D009249:NADP / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014981:Xenopus / Q000196:embryology
chemical_list: D002147:Calmodulin; D017931:DNA Primers; D009249:NADP; D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase
keywords: NAD kinase; NADP; calcium signaling; deuterostome animals; metabolism