Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis.

Hdl Handle:
http://hdl.handle.net/10675.2/22
Title:
Physical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis.
Authors:
Guo, Dehuang; Ling, Jennifer X; Wang, Mong-Heng; She, Jin-Xiong; Gu, Jianguo; Wang, Cong-Yi
Abstract:
Divalent metal ions such as copper, manganese, and cobalt are essential for cell development, differentiation, function and survival. These essential metal ions are delivered into intracellular domains as cofactors for enzymes involved in neuropeptide and neurotransmitter synthesis, superoxide metabolism, and other biological functions in a target specific fashion. Altering the homeostasis of these essential metal ions is known to connect to a number of human diseases including Alzheimer disease, amyotrophic lateral sclerosis, and pain. It remains unclear how these essential metal ions are delivered to intracellular targets in mammalian cells. Here we report that rat spinal cord dorsal horn neurons express ACDP4, a member of Ancient Conserved Domain Protein family. By screening a pretransformed human fetal brain cDNA library in a yeast two-hybrid system, we have identified that ACDP4 specifically interacts with COX11, an intracellular metal ion chaperone. Ectopic expression of ACDP4 in HEK293 cells resulted in enhanced toxicity to metal ions including copper, manganese, and cobalt. The metal ion toxicity became more pronounced when ACDP4 and COX11 were co-expressed ectopically in HEK293 cells, suggesting a functional coupling between them. Our results indicate a role of ACDP4 in metal ion homeostasis and toxicity. This is the first report revealing a functional aspect of this ancient conserved domain protein family. We propose that ACDP is a family of transporter protein or chaperone proteins for delivering essential metal ions in different mammalian tissues. The expression of ACDP4 on spinal cord dorsal horn neurons may have implications in sensory neuron functions under physiological and pathological conditions.
Citation:
Mol Pain. 2005 Apr 19; 1:15
Issue Date:
16-Jan-2008
URI:
http://hdl.handle.net/10675.2/22
DOI:
10.1186/1744-8069-1-15
PubMed ID:
15840172
PubMed Central ID:
PMC1097757
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
ISSN:
1744-8069
Appears in Collections:
Center for Biotechnology and Genomic Medicine: Faculty Research and Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorGuo, Dehuangen_US
dc.contributor.authorLing, Jennifer Xen_US
dc.contributor.authorWang, Mong-Hengen_US
dc.contributor.authorShe, Jin-Xiongen_US
dc.contributor.authorGu, Jianguoen_US
dc.contributor.authorWang, Cong-Yien_US
dc.date.accessioned2010-09-24T20:59:22Z-
dc.date.available2010-09-24T20:59:22Z-
dc.date.issued2008-01-16en_US
dc.identifier.citationMol Pain. 2005 Apr 19; 1:15en_US
dc.identifier.issn1744-8069en_US
dc.identifier.pmid15840172en_US
dc.identifier.doi10.1186/1744-8069-1-15en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/22-
dc.description.abstractDivalent metal ions such as copper, manganese, and cobalt are essential for cell development, differentiation, function and survival. These essential metal ions are delivered into intracellular domains as cofactors for enzymes involved in neuropeptide and neurotransmitter synthesis, superoxide metabolism, and other biological functions in a target specific fashion. Altering the homeostasis of these essential metal ions is known to connect to a number of human diseases including Alzheimer disease, amyotrophic lateral sclerosis, and pain. It remains unclear how these essential metal ions are delivered to intracellular targets in mammalian cells. Here we report that rat spinal cord dorsal horn neurons express ACDP4, a member of Ancient Conserved Domain Protein family. By screening a pretransformed human fetal brain cDNA library in a yeast two-hybrid system, we have identified that ACDP4 specifically interacts with COX11, an intracellular metal ion chaperone. Ectopic expression of ACDP4 in HEK293 cells resulted in enhanced toxicity to metal ions including copper, manganese, and cobalt. The metal ion toxicity became more pronounced when ACDP4 and COX11 were co-expressed ectopically in HEK293 cells, suggesting a functional coupling between them. Our results indicate a role of ACDP4 in metal ion homeostasis and toxicity. This is the first report revealing a functional aspect of this ancient conserved domain protein family. We propose that ACDP is a family of transporter protein or chaperone proteins for delivering essential metal ions in different mammalian tissues. The expression of ACDP4 on spinal cord dorsal horn neurons may have implications in sensory neuron functions under physiological and pathological conditions.en_US
dc.rightsThe PMC Open Access Subset is a relatively small part of the total collection of articles in PMC. Articles in the PMC Open Access Subset are still protected by copyright, but are made available under a Creative Commons or similar license that generally allows more liberal redistribution and reuse than a traditional copyrighted work. Please refer to the license statement in each article for specific terms of use. The license terms are not identical for all articles in this subset.en_US
dc.subject.meshAnimalsen_US
dc.subject.meshCell Lineen_US
dc.subject.meshConserved Sequenceen_US
dc.subject.meshCytoplasm / physiologyen_US
dc.subject.meshElectron Transport Complex IV / physiologyen_US
dc.subject.meshHomeostasis / physiologyen_US
dc.subject.meshHumansen_US
dc.subject.meshIon Transport / physiologyen_US
dc.subject.meshMetals / metabolismen_US
dc.subject.meshMolecular Chaperones / physiologyen_US
dc.subject.meshPosterior Horn Cells / metabolismen_US
dc.subject.meshProtein Structure, Tertiaryen_US
dc.subject.meshRatsen_US
dc.subject.meshRats, Sprague-Dawleyen_US
dc.titlePhysical interaction and functional coupling between ACDP4 and the intracellular ion chaperone COX11, an implication of the role of ACDP4 in essential metal ion transport and homeostasis.en_US
dc.typeJournal Articleen_US
dc.typeResearch Support, N.I.H., Extramuralen_US
dc.typeResearch Support, Non-U.S. Gov'ten_US
dc.identifier.pmcidPMC1097757en_US
dc.contributor.corporatenameCenter for Biotechnology and Genomic Medicineen_US
dc.contributor.corporatenameDepartment of Physiologyen_US

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