Regulation of murine copper homeostasis by members of the COMMD protein family [RESEARCH ARTICLE]

In this study, we examined copper homeostasis in enterocyte-specific and hepatocyte-specific COMMD gene-deficient mice. We found that, in contrast to effects in cell lines in culture, COMMD protein deficiency induced minimal changes in ATP7A in enterocytes and did not lead to altered copper levels under low- or high-copper diets, suggesting that regulation of ATP7A in enterocytes is not of physiological consequence. By contrast, deficiency of any of three COMMD genes (Commd1, Commd6 or Commd9) resulted in hepatic copper accumulation under high-copper diets. We found that each of these deficiencies caused destabilization of the entire CCC complex and suggest that this might explain their shared phenotype. Overall, we conclude that the CCC complex plays an important role in ATP7B endosomal recycling and function.

Source: DMM Disease Models and Mechanisms - January 7, 2021 Category: Biomedical Science Authors: Singla, A., Chen, Q., Suzuki, K., Song, J., Fedoseienko, A., Wijers, M., Lopez, A., Billadeau, D. D., van de Sluis, B., Burstein, E. Tags: RESEARCH ARTICLE Source Type: research