Atp7a determines a hierarchy of copper metabolism essential for notochord development - PubMed (original) (raw)
Atp7a determines a hierarchy of copper metabolism essential for notochord development
Bryce A Mendelsohn et al. Cell Metab. 2006 Aug.
Free article
Abstract
The critical developmental and genetic requirements of copper metabolism during embryogenesis are unknown. Utilizing a chemical genetic screen in zebrafish, we identified small molecules that perturb copper homeostasis. Our findings reveal a role for copper in notochord formation and demonstrate a hierarchy of copper metabolism within the embryo. To elucidate these observations, we interrogated a genetic screen for embryos phenocopied by copper deficiency, identifying calamity, a mutant defective in the zebrafish ortholog of the Menkes disease gene (atp7a). Copper metabolism in calamity is restored by human ATP7A, and transplantation experiments reveal that atp7a functions cell autonomously, findings with important therapeutic implications. The gene dosage of atp7a determines the sensitivity to copper deprivation, revealing that the observed developmental hierarchy of copper metabolism is informed by specific genetic factors. Our data provide insight into the developmental pathophysiology of copper metabolism and suggest that suboptimal copper metabolism may contribute to birth defects.
Comment in
- Precious metal economy.
Merchant SS, Sagasti A. Merchant SS, et al. Cell Metab. 2006 Aug;4(2):99-101. doi: 10.1016/j.cmet.2006.07.003. Cell Metab. 2006. PMID: 16890535 Review.
Similar articles
- Zebrafish mutants calamity and catastrophe define critical pathways of gene-nutrient interactions in developmental copper metabolism.
Madsen EC, Gitlin JD. Madsen EC, et al. PLoS Genet. 2008 Nov;4(11):e1000261. doi: 10.1371/journal.pgen.1000261. Epub 2008 Nov 14. PLoS Genet. 2008. PMID: 19008952 Free PMC article. - Zebrafish sod1 and sp1 expression are modulated by the copper ATPase gene atp7a in response to intracellular copper status.
Chen HR, Yang HC, Hsieh DJ, Liu Z, Tsai KJ. Chen HR, et al. Chem Biol Interact. 2011 Feb 1;189(3):192-7. doi: 10.1016/j.cbi.2010.12.003. Epub 2010 Dec 15. Chem Biol Interact. 2011. PMID: 21167140 - PCR-cloning of tilapia ATP7A cDNA and its mRNA levels in tissues of tilapia following copper administrations.
Chen DS, Chan KM. Chen DS, et al. Aquat Toxicol. 2011 Oct;105(3-4):717-27. doi: 10.1016/j.aquatox.2011.09.011. Epub 2011 Sep 19. Aquat Toxicol. 2011. PMID: 21996258 - Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes.
de Bie P, Muller P, Wijmenga C, Klomp LW. de Bie P, et al. J Med Genet. 2007 Nov;44(11):673-88. doi: 10.1136/jmg.2007.052746. Epub 2007 Aug 23. J Med Genet. 2007. PMID: 17717039 Free PMC article. Review. - Small amounts of functional ATP7A protein permit mild phenotype.
Møller LB. Møller LB. J Trace Elem Med Biol. 2015;31:173-7. doi: 10.1016/j.jtemb.2014.07.022. Epub 2014 Aug 8. J Trace Elem Med Biol. 2015. PMID: 25172213 Review.
Cited by
- Function Over Form: Modeling Groups of Inherited Neurological Conditions in Zebrafish.
Kozol RA, Abrams AJ, James DM, Buglo E, Yan Q, Dallman JE. Kozol RA, et al. Front Mol Neurosci. 2016 Jul 7;9:55. doi: 10.3389/fnmol.2016.00055. eCollection 2016. Front Mol Neurosci. 2016. PMID: 27458342 Free PMC article. Review. - Juxtaposition of chemical and mutation-induced developmental defects in zebrafish reveal a copper-chelating activity for kalihinol F.
Sandoval IT, Manos EJ, Van Wagoner RM, Delacruz RG, Edes K, Winge DR, Ireland CM, Jones DA. Sandoval IT, et al. Chem Biol. 2013 Jun 20;20(6):753-63. doi: 10.1016/j.chembiol.2013.05.008. Chem Biol. 2013. PMID: 23790486 Free PMC article. - The genetics of essential metal homeostasis during development.
Kambe T, Weaver BP, Andrews GK. Kambe T, et al. Genesis. 2008 Apr;46(4):214-28. doi: 10.1002/dvg.20382. Genesis. 2008. PMID: 18395838 Free PMC article. Review. - Essential role for fibrillin-2 in zebrafish notochord and vascular morphogenesis.
Gansner JM, Madsen EC, Mecham RP, Gitlin JD. Gansner JM, et al. Dev Dyn. 2008 Oct;237(10):2844-61. doi: 10.1002/dvdy.21705. Dev Dyn. 2008. PMID: 18816837 Free PMC article. - Animal models of Wilson disease.
Reed E, Lutsenko S, Bandmann O. Reed E, et al. J Neurochem. 2018 Aug;146(4):356-373. doi: 10.1111/jnc.14323. Epub 2018 Jun 26. J Neurochem. 2018. PMID: 29473169 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
- T32 GM07200/GM/NIGMS NIH HHS/United States
- P30 DK056341/DK/NIDDK NIH HHS/United States
- P30 DK056341-06/DK/NIDDK NIH HHS/United States
- DK44464/DK/NIDDK NIH HHS/United States
- HD39952/HD/NICHD NIH HHS/United States
- GM55101/GM/NIGMS NIH HHS/United States
- P30 DK056341-05S2/DK/NIDDK NIH HHS/United States
- GM56988/GM/NIGMS NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases