Functional understanding of the versatile protein copper metabolism MURR1 domain 1 (COMMD1) in copper homeostasis

Ann N Y Acad Sci. 2014 May:1314:6-14. doi: 10.1111/nyas.12353. Epub 2014 Feb 12.

Abstract

Copper is an important cofactor in numerous biological processes in all living organisms. However, excessive copper can be extremely toxic, so it is vital that the copper level within a cell is tightly regulated. The damaging effect of copper is seen in several hereditary forms of copper toxicity in humans and animals. At present, Wilson's disease is the best-described and best-studied copper-storage disorder in humans; it is caused by mutations in the ATP7B gene. In dogs, a mutation in the COMMD1 gene has been found to be associated with copper toxicosis. Using a liver-specific Commd1 knockout mouse, the biological role of Commd1 in copper homeostasis has been confirmed. Yet, the exact mechanism by which COMMD1 regulates copper homeostasis is still unknown. Here, we give an overview of the current knowledge and perspectives on the molecular function of COMMD1 in copper homeostasis.

Keywords: COMMD1; copper homeostasis; intracellular trafficking; vesicle transport.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism
  • Animals
  • Biological Transport
  • Cation Transport Proteins / genetics
  • Cation Transport Proteins / metabolism
  • Copper / blood
  • Copper / metabolism*
  • Copper / toxicity*
  • Copper-Transporting ATPases
  • Dogs
  • Hepatolenticular Degeneration / genetics
  • Hepatolenticular Degeneration / metabolism*
  • Homeostasis / genetics
  • Humans
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism*
  • Metal Metabolism, Inborn Errors / genetics
  • Metal Metabolism, Inborn Errors / metabolism*
  • Mice
  • Mice, Knockout

Substances

  • Adaptor Proteins, Signal Transducing
  • COMMD1 protein, human
  • Cation Transport Proteins
  • Commd1 protein, mouse
  • Copper
  • Adenosine Triphosphatases
  • ATP7B protein, human
  • Copper-Transporting ATPases

Supplementary concepts

  • Copper Toxicosis, Idiopathic