In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-03-29)
Abstract:
People need a source of copper in their diet because this nutrient is used to produce the pigment in hair and skin, the connective tissue in tendons and ligaments, and some of the small molecules that allow brain cells to communicate. There is an ideal range of copper that allows cells to carry out these processes. Both too much and too little copper can have negative effects on health, particularly related to how the brain works. Cells contain multiple proteins that bind to copper and transport it wherever it is needed. People with mutations that mean they lack one of these copper transporters, ATP7A, often have serious damage to their nervous system that cannot be explained by the current understanding of how this protein works. Comstra et al. set out to establish a comprehensive list of proteins that interact with ATP7A to better understand how this transporter works and how it is regulated. The search revealed that ATP7A interacts with hundreds of proteins present in different compartments within cells, many of which had not previously been associated with balancing copper levels in cells and the body. Like ATP7A, many of these proteins (or the protein complexes that contain them) are known to affect nerves and brain activity when they are mutated. Next, Comstra et al. engineered human cells grown in the laboratory to lack one of the protein complexes that interacts with ATP7A, the COG complex. Cells without this protein complex had 50% less ATP7A than normal human cells and very low levels of copper too. These mutant cells also had problems generating the energy that they need, because the structures in cells that provide them with energy – the mitochondria – were impaired; adding copper to the cells improved the activity of their mitochondria. Mutations in the COG complex cause the brain to develop abnormally, and the finding that deleting the COG complex from cells causes copper deficiency now helps to explain why. Further characterization of the proteins that interact with ATP7A and the COG complex will contribute to our understanding of how cells regulate copper and how copper levels affect the brain.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.24722.001
DOI:
10.7554/eLife.24722.002
DOI:
10.7554/eLife.24722.003
DOI:
10.7554/eLife.24722.004
DOI:
10.7554/eLife.24722.005
DOI:
10.7554/eLife.24722.006
DOI:
10.7554/eLife.24722.007
DOI:
10.7554/eLife.24722.008
DOI:
10.7554/eLife.24722.009
DOI:
10.7554/eLife.24722.010
DOI:
10.7554/eLife.24722.011
DOI:
10.7554/eLife.24722.012
DOI:
10.7554/eLife.24722.013
DOI:
10.7554/eLife.24722.014
DOI:
10.7554/eLife.24722.015
DOI:
10.7554/eLife.24722.020
DOI:
10.7554/eLife.24722.021
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3