The study highlights dramatic differences in the use of copper in developing or mature neurons, say the multi-national team of researchers.
“The cells make a decision on how to distribute copper because its more or less limited so it needs to be used where it’s needed,” researcher Professor Lutsenko from John Hopkins University in Baltimore told us.
Copper is an essential trace element vital to humans, and mechanisms within the body ensure there is a constant flow of available copper while preventing excess. Both deficiency and excess can have effects on health.
Previous studies have shown that developing neurons in the brain need copper to differentiate and that there is a spike in the brain’s copper levels at a certain stage of development.
In the study published in Nature Communications, scientists infected chicken embryos at different stages of development with a tiny sensor that changes its fluorescence to signal the ‘redox’ state of cells - the transfer of electrons that drive many processes in the body.
The sensor was used to investigate how differentiating neurons regulate copper within the cell.
Neuronal cells in the brain need copper for their activities and metabolism, and copper-requiring enzymes (proteins) are located in different cellular compartments the copper needs to be directed to.
This is important for regulation of chemicals that control things like decision making, moods and addiction and many metabolic processes essential to life.
As the cells are growing they need a lot of energy so copper is used elsewhere, she said.
“When they become neurons and have acquired an identity and start making these important copper dependant enzymes, then copper has to be redirected to the right place.”
The researchers found that the protein Atox1, which acts as a copper shuttle, has its binding site only partially available as the cells are growing. Yet if the cell becomes a neuron this changes.
“If cells fully differentiate and become mature the environment changes in such a way that now the shuttle Atox1 is fully reduced and fully available to bind copper and deliver it to where it is needed within the secretory pathway to copper dependant enzymes.”
‘An effect on multiple pathways’
Lutsenko said in ageing and diseases such as Alzheimer’s and Parkinson’s - where there is oxidative stress and the normal redox balance may be changing - this could lead to less copper being delivered to the dependant enzymes and could have an effect on multiple pathways and processes downstream.
The researchers now plan to examine whether they see this in ageing cells or brain conditions.
Source: Nature Communications
Published online ahead of print, doi: 10.1038/ncomms10640
“Neuronal differentiation is associated with a redox-regulated increase of copper ﬂow to the secretory pathway”
Authors: Y. Hatori et al.