Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development

AUTOR(ES)

Lee, Jaekwon

FONTE

The National Academy of Sciences

RESUMO

The trace metal copper (Cu) plays an essential role in biology as a cofactor for many enzymes that include Cu, Zn superoxide dismutase, cytochrome oxidase, ceruloplasmin, lysyl oxidase, and dopamine β-hydroxylase. Consequently, Cu transport at the cell surface and the delivery of Cu to intracellular compartments are critical events for a wide variety of biological processes. The components that orchestrate intracellular Cu trafficking and their roles in Cu homeostasis have been elucidated by the studies of model microorganisms and by the characterizations of molecular basis of Cu-related genetic diseases, including Menkes disease and Wilson disease. However, little is known about the mechanisms for Cu uptake at the plasma membrane and the consequences of defects in this process in mammals. Here, we show that the mouse Ctr1 gene encodes a component of the Cu transport machinery and that mice heterozygous for Ctr1 exhibit tissue-specific defects in copper accumulation and in the activities of copper-dependent enzymes. Mice completely deficient for Ctr1 exhibit profound growth and developmental defects and die in utero in mid-gestation. These results demonstrate a crucial role for Cu acquisition through the Ctr1 transporter for mammalian Cu homeostasis and embryonic development.

Documentos Relacionados

• The copper transporter CTR1 provides an essential function in mammalian embryonic development
• Uptake of the anticancer drug cisplatin mediated by the copper transporter Ctr1 in yeast and mammals
• Mammalian Copper Chaperone Cox17p Has an Essential Role in Activation of Cytochrome c Oxidase and Embryonic Development
• Copper-dependent Recycling of hCTR1, the Human High Affinity Copper Transporter*
• Essential role for Max in early embryonic growth and development