The copper chaperone CCS is abundant in neurons and astrocytes in human and rodent brain

Copper trafficking in mammalian cells is highly regulated. CCS is a copper chaperone that donates copper to the antioxidant enzyme copper/zinc superox ide dismutase 1 (SOD 1). Mutations of SOD1 are responsible for similar to 2 0% of familial amyotrophic lateral sclerosis (FALS). Monospecific antibodie s 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 i n particularly high concentrations in kidney and liver. In brain and spinal cord, CCS was found throughout the neuropil, with expression largely confi ned to neurons and some astrocytes. Like SOD1, CCS immunoreactivity was int ense in Purkinje cells, deep cerebellar neurons, and pyramidal cortical neu rons, whereas in spinal cord, CCS was highly expressed in motor neurons. In cortical neurons, CCS was present in the soma and proximal dendrites, as w ell 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.