title: A copper-regulated transporter required for copper acquisition, pigmentation, and specific stages of development in Drosophila melanogaster.
abstract: The trace element copper is required for normal growth and development, serving as an essential catalytic co-factor for enzymes involved in energy generation, oxidative stress protection, neuropeptide maturation, and other fundamental processes. In yeast and mammals copper acquisition occurs through the action of the Ctr1 family of high affinity copper transporters. Here we describe studies using Drosophila melanogaster to investigate the role of copper acquisition through Ctr1 in normal growth and development. Three distinct Drosophila Ctr1 genes (Ctr1A, Ctr1B, and Ctr1C) have been identified, which have unique expression patterns over the course of development. Interestingly, Ctr1B, which is expressed exclusively during the late embryonic and larval stages of development, is transcriptionally activated in response to nutritionally induced copper deprivation and down-regulated in response to copper adequacy. The generation of Ctr1B mutant flies results in decreased larval copper accumulation, marked body pigmentation defects that parallel defects in tyrosinase activity, and specific developmental arrest under conditions of both nutritional copper limitation and excess. These studies establish that copper acquisition through the Drosophila Ctr1B transporter is crucial for normal growth and in early and specific stages of metazoan development.
authors.affiliation: Department of Biological Chemistry, University of Michigan Medical School, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhou
authors.forename: Ken M
authors.initials: KM
authors.lastname: Cadigan
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Thiele
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport; D027682:Cation Transport Proteins; D003001:Cloning, Molecular; D003300:Copper / Q000378:metabolism*; D000079923:Copper Transporter 1; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000737:chemistry* / Q000502:physiology*; D004331:Drosophila melanogaster / Q000196:embryology*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D016678:Genome; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000502:physiology*; D008957:Models, Genetic; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012313:RNA / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D015533:Transcriptional Activation
chemical_list: C490078:CTR1 protein, S cerevisiae; D027682:Cation Transport Proteins; D000079923:Copper Transporter 1; D029721:Drosophila Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D029701:Saccharomyces cerevisiae Proteins; D012313:RNA; D003300:Copper; D014442:Monophenol Monooxygenase