title: The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain.
abstract: Copper trafficking in mammalian cells is highly regulated. CCS is a copper chaperone that donates copper to the antioxidant enzyme copper/zinc superoxide dismutase 1 (SOD 1). Mutations of SOD1 are responsible for approximately 20% of familial amyotrophic lateral sclerosis (FALS). Monospecific antibodies were generated to evaluate the localization and cellular distribution of this copper chaperone in human and mouse brain as well as other organs. CCS is found to be ubiquitously expressed by multiple tissues and is present in particularly high concentrations in kidney and liver. In brain and spinal cord, CCS was found throughout the neuropil, with expression largely confined to neurons and some astrocytes. Like SOD1, CCS immunoreactivity was intense in Purkinje cells, deep cerebellar neurons, and pyramidal cortical neurons, whereas in spinal cord, CCS was highly expressed in motor neurons. In cortical neurons, CCS was present in the soma and proximal dendrites, as well as some axons. Although the distribution of CCS paralleled that of SOD1, there was a 12-30-fold molar excess of SOD1 over CCS. That both SOD1 and CCS are present, together, in cells that degenerate in ALS also emphasizes the potential role of CCS in mutant SOD1-mediated toxicity.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Rothstein
authors.forename: M
authors.initials: M
authors.lastname: Dykes-Hoberg
authors.forename: L B
authors.initials: LB
authors.lastname: Corson
authors.forename: M
authors.initials: M
authors.lastname: Becker
authors.forename: D W
authors.initials: DW
authors.lastname: Cleveland
authors.forename: D L
authors.initials: DL
authors.lastname: Price
authors.forename: V C
authors.initials: VC
authors.lastname: Culotta
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism; D000818:Animals; D000906:Antibodies; D001253:Astrocytes / Q000737:chemistry* / Q000201:enzymology; D001923:Brain Chemistry / Q000502:physiology*; D018833:Chaperonins / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D003300:Copper / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018832:Molecular Chaperones / Q000032:analysis / Q000276:immunology / Q000378:metabolism*; D009046:Motor Neurons / Q000737:chemistry* / Q000201:enzymology; D009420:Nervous System / Q000166:cytology; D051381:Rats; D013482:Superoxide Dismutase / Q000032:analysis
chemical_list: D000906:Antibodies; C114678:CCS protein, human; C491962:Ccs protein, mouse; C491961:Ccs protein, rat; D018832:Molecular Chaperones; D003300:Copper; D013482:Superoxide Dismutase; D018833:Chaperonins