Mobilization of intracellular copper stores by the Ctr2 vacuolar copper transporter

Erin M. Rees, Jaekwon Lee, Dennis J. Thiele

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Copper plays an essential role in processes including signaling to the transcription and protein trafficking machinery, oxidative phosphorylation, iron mobilization, neuropeptide maturation, and normal development. Whereas much is known about intracellular mobilization of ions such as calcium, little information is available on how eukaryotic cells mobilize intracellular copper stores. We describe a mechanism by which the Saccharomyces cerevisiae Ctr2 protein provides bioavailable copper via mobilization of intracellular copper stores. Whereas Ctr2 exhibits structural similarity to the Ctrl plasma membrane copper importer, microscopic and biochemical fractionation studies localize Ctr2 to the vacuole membrane. We demonstrate that Ctr2 mobilizes vacuolar copper stores in a manner dependent on amino acid residues conserved between the Ctrl and Ctr2 copper transport family and that cfr2Δ mutants hyper-accumulate vacuolar copper. Furthermore, a Ctr2 mutant that is mislocalized to the plasma membrane stimulates extracellular copper uptake, supporting a direct role for Ctr2 in copper transport across membranes. These studies identify a novel mechanism for copper mobilization and suggest that organisms cope with copper deprivation via the use of intracellular vesicular stores.

Original languageEnglish (US)
Pages (from-to)54221-54229
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number52
DOIs
StatePublished - Dec 24 2004

Fingerprint

Copper
Cell membranes
Cell Membrane
Saccharomyces cerevisiae Proteins
Membranes
Oxidative Phosphorylation
Eukaryotic Cells
Protein Transport
Transcription
Fractionation
Vacuoles
Neuropeptides
Yeast
Machinery
Proteins
Iron
Ions
Calcium
Amino Acids

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Mobilization of intracellular copper stores by the Ctr2 vacuolar copper transporter. / Rees, Erin M.; Lee, Jaekwon; Thiele, Dennis J.

In: Journal of Biological Chemistry, Vol. 279, No. 52, 24.12.2004, p. 54221-54229.

Research output: Contribution to journalArticle

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