Characterization of mouse embryonic cells deficient in the Ctr1 high affinity copper transporter: Identification of a Ctr1-independent copper transport system

Jaekwon Lee, Michael J. Petris, Dennis J. Thiele

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

The trace metal copper is an essential cofactor for a number of enzymes that have critical roles in biological processes, but it is highly toxic when allowed to accumulate in excess of cellular needs. Consequently, homeostatic copper metabolism is maintained by molecules involved in copper uptake, distribution, excretion, and incorporation into copper-requiring enzymes. Previously, we reported that overexpression of the human or mouse Ctr1 copper transporter stimulates copper uptake in mammalian cells, and deletion of one Ctr1 allele in mice gives rise to tissue-specific defects in copper accumulation and in the activities of copper-dependent enzymes. To investigate the physiological roles for mammalian Ctr1 protein in cellular copper metabolism, we characterized wild type, Ctr1 heterozygous, and Ctr1 homozygous knock-out cells isolated from embryos obtained by the inter-cross of Ctr1 heterozygous mice. Ctr1-deficient mouse embryonic cells are viable but exhibit significant defects in copper uptake and accumulation and in copper-dependent enzyme activities. Interestingly, Ctr1-deficient cells exhibit ∼30% residual copper transport activity that is saturable, with a Km of ∼10 μM, with biochemical features distinct from that of Ctr1. These observations demonstrate that, although Ctr1 is critical for both cellular copper uptake and embryonic development, mammals possess additional biochemically distinct functional copper transport activities.

Original languageEnglish (US)
Pages (from-to)40253-40259
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number43
DOIs
StatePublished - Oct 25 2002

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Copper
Enzymes
Metabolism
Biological Phenomena
Defects
Mammals
Poisons
Enzyme activity
Embryonic Development
Embryonic Structures
Metals
Alleles
Cells
Tissue
Molecules

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Characterization of mouse embryonic cells deficient in the Ctr1 high affinity copper transporter : Identification of a Ctr1-independent copper transport system. / Lee, Jaekwon; Petris, Michael J.; Thiele, Dennis J.

In: Journal of Biological Chemistry, Vol. 277, No. 43, 25.10.2002, p. 40253-40259.

Research output: Contribution to journalArticle

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