A novel role for the immunophilin FKBP52 in copper transport

Reiko Sanokawa-Akakura, Huachang Dai, Shin Akakura, David Weinstein, J. Eduardo Fajardo, Steven E. Lang, Scott Wadsworth, John Siekierka, Raymond B. Birge

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Abstract

FK506-binding protein 52 (FKBP52) is an immunophilin that possesses peptidylprolyl cis/trans-isomerase (PPIase) activity and is a component of a subclass of steroid hormone receptor complexes. Several recent studies indicate that immunophilins can regulate neuronal survival and nerve regeneration although the molecular mechanisms are poorly understood. To investigate the function of FKBP52 in the nervous system, we employed a yeast two-hybrid strategy using the PPIase domain (domain I) as bait to screen a neonatal rat dorsal root ganglia cDNA expression library. We identified an interaction between FKBP52 domain I and Atox1, a copper-binding metallochaperone, Atox1 interacts with Menkes disease protein and Wilson disease protein (WD) and functions in copper efflux. The interaction between FKBP52 and Atox1 was observed in both glutathione S-transferase pull-down experiments and when proteins were ectopically expressed in human embryonic kidney (HEK) 293T cells and was sensitive to FK506. Interestingly, the FKBP52/Atox1 interaction was enhanced when HEK 293T cells were cultured in copper-supplemented medium and decreased in the presence of the copper chelator, bathocuproine disulfate, suggesting that the interaction is regulated in part by intracellular copper. Overexpression of FKBP52 increased rapid copper efflux in 64Cu-loaded cells, as did the overexpression of WD transporter. Taken together, our present findings suggest that FKBP52 is a component of the copper efflux machinery, and in so, may also promote neuroprotection from copper toxicity.

Original languageEnglish
Pages (from-to)27845-27848
Number of pages4
JournalJournal of Biological Chemistry
Volume279
Issue number27
DOIs
StatePublished - 2 Jul 2004

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Immunophilins
Tacrolimus Binding Proteins
Copper
cis-trans-Isomerases
Peptidylprolyl Isomerase
HEK293 Cells
Metallochaperones
Steroid hormones
Menkes Kinky Hair Syndrome
Kidney
Nerve Regeneration
Steroid Receptors
Spinal Ganglia
Neurology
Tacrolimus
Chelating Agents
Glutathione Transferase
Gene Library
Yeast
Nervous System

Cite this

Sanokawa-Akakura, R., Dai, H., Akakura, S., Weinstein, D., Fajardo, J. E., Lang, S. E., ... Birge, R. B. (2004). A novel role for the immunophilin FKBP52 in copper transport. Journal of Biological Chemistry, 279(27), 27845-27848. https://doi.org/10.1074/jbc.C400118200
Sanokawa-Akakura, Reiko ; Dai, Huachang ; Akakura, Shin ; Weinstein, David ; Fajardo, J. Eduardo ; Lang, Steven E. ; Wadsworth, Scott ; Siekierka, John ; Birge, Raymond B. / A novel role for the immunophilin FKBP52 in copper transport. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 27. pp. 27845-27848.
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Sanokawa-Akakura, R, Dai, H, Akakura, S, Weinstein, D, Fajardo, JE, Lang, SE, Wadsworth, S, Siekierka, J & Birge, RB 2004, 'A novel role for the immunophilin FKBP52 in copper transport', Journal of Biological Chemistry, vol. 279, no. 27, pp. 27845-27848. https://doi.org/10.1074/jbc.C400118200

A novel role for the immunophilin FKBP52 in copper transport. / Sanokawa-Akakura, Reiko; Dai, Huachang; Akakura, Shin; Weinstein, David; Fajardo, J. Eduardo; Lang, Steven E.; Wadsworth, Scott; Siekierka, John; Birge, Raymond B.

In: Journal of Biological Chemistry, Vol. 279, No. 27, 02.07.2004, p. 27845-27848.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Sanokawa-Akakura, Reiko

AU - Dai, Huachang

AU - Akakura, Shin

AU - Weinstein, David

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AU - Lang, Steven E.

AU - Wadsworth, Scott

AU - Siekierka, John

AU - Birge, Raymond B.

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Sanokawa-Akakura R, Dai H, Akakura S, Weinstein D, Fajardo JE, Lang SE et al. A novel role for the immunophilin FKBP52 in copper transport. Journal of Biological Chemistry. 2004 Jul 2;279(27):27845-27848. https://doi.org/10.1074/jbc.C400118200