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.
MetadataShow full item record
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.
CitationMol Pain. 2005 Apr 19; 1:15
- Manganese toxicity and Saccharomyces cerevisiae Mam3p, a member of the ACDP (ancient conserved domain protein) family.
- Authors: Yang M, Jensen LT, Gardner AJ, Culotta VC
- Issue date: 2005 Mar 15
- Molecular cloning and characterization of the mouse Acdp gene family.
- Authors: Wang CY, Yang P, Shi JD, Purohit S, Guo D, An H, Gu JG, Ling J, Dong Z, She JX
- Issue date: 2004 Jan 15
- Structure and metal ion binding of the first transmembrane domain of DMT1.
- Authors: Wang D, Song Y, Li J, Wang C, Li F
- Issue date: 2011 Jun
- Metal ion transporters and homeostasis.
- Authors: Nelson N
- Issue date: 1999 Aug 16
- The neuropeptide tyrosine Y1R is expressed in interneurons and projection neurons in the dorsal horn and area X of the rat spinal cord.
- Authors: Brumovsky P, Hofstetter C, Olson L, Ohning G, Villar M, Hökfelt T
- Issue date: 2006