Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 112, Issue 5, Pages 1386-1391Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1417290112
Keywords
metabolism; NADP; calcium signaling; deuterostome animals; NAD kinase
Categories
Funding
- National Science Foundation (NSF)'s Norwegian Research Opportunity initiative
- Norwegian Research Council [172219/V40]
- Wellcome Trust Program
- Healing Foundation
- NSF
- Biotechnology and Biological Sciences Research Council [BB/K000942/1, BB/D018110/1, BB/G013721/1] Funding Source: researchfish
- Medical Research Council [MR/L007525/1] Funding Source: researchfish
- BBSRC [BB/D018110/1, BB/K000942/1, BB/G013721/1] Funding Source: UKRI
- MRC [MR/L007525/1] Funding Source: UKRI
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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 Ca2+/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.
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