NAD kinase controls animal NADP biosynthesis and is modulated via evolutionarily divergent calmodulin-dependent mechanisms.

Nick R Love, Nadine Pollak, Christian Dölle, Marc Niere, Yaoyao Chen, Paola Oliveri, Enrique Amaya, Sandip Patel, Mathias Ziegler

    Research output: Contribution to journalArticlepeer-review

    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.
    Original languageEnglish
    Pages (from-to)1386-1391
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume112
    Issue number5
    DOIs
    Publication statusPublished - 20 Jan 2015

    Keywords

    • NAD kinase
    • NADP
    • calcium signaling
    • deuterostome animals
    • metabolism

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