Biologists Identify Crucial Molecule that Regulates Breathing

A team of researchers at the University of Warwick, UK, has identified Connexin26 (Cx26) as a key molecule that reacts to carbon dioxide (CO2) in our bodies and activates breathing. The study is published in the journal Proceedings of the Royal Society B.

CO2-dependent dye loading of HeLa cells expressing Cx26 from human. The top images (green) show the CO2-dependent loading of 5(6)-CBF at three different levels of PCO2. The Cx26 was tagged at the C-terminal with mCherry. The bottom images (red) in each panel show the mCherry fluorescence and hence Cx26 expression corresponding to the cells that were loaded in the images above. Image credit: Elizabeth de Wolf et al, doi: 10.1098/rspb.2016.2723.

CO2-dependent dye loading of HeLa cells expressing Cx26 from human. The top images (green) show the CO2-dependent loading of 5(6)-CBF at three different levels of PCO2. The Cx26 was tagged at the C-terminal with mCherry. The bottom images (red) in each panel show the mCherry fluorescence and hence Cx26 expression corresponding to the cells that were loaded in the images above. Image credit: Elizabeth de Wolf et al, doi: 10.1098/rspb.2016.2723.

Cx26 molecules (also known as Gap junction beta-2, GJB2) detect levels of CO2 in the blood-stream, and when levels reach a certain point, they tell our bodies to excrete the CO2 and take in oxygen – the vital life-preserving process that allows us to breathe, and creates blood flow to the brain.

Without this essential molecular function, harmful levels of CO2 would remain in the bloodstream, making breathing difficult or impossible.

Mutations in Cx26 are directly connected to a number of serious conditions – ranging from congenital deafness, to respiratory conditions, and serious syndromes that affect skin, vision and hearing.

As Cx26 is vital to breathing well, people carrying these mutations may be at risk of sleep apnoea.

Identifying these mutations and working out how to restore the molecule to its normal function could lead to effective, targeted, personalized treatments to mitigate these risks and improve quality of life.

“Important molecules with universal physiological functions are shaped by evolution,” said lead author Prof. Nicholas Dale, from the School of Life Sciences at the University of Warwick.

“We have exploited this simple fact to show that the CO2-binding characteristics of Cx26 are important in our bodies too.”

“This is likely to open up new ways to identify and treat people at risk of sleep apneas.”

Different animals have varying levels of sensitivity to CO2.

Prof. Dale and his colleagues, Elizabeth de Wolf and Jonathan Cook, exploited this idea to see whether the properties of Cx26 matched the physiological requirements of: birds, which fly at high-altitude and can tolerate low levels of CO2; humans and rats which are broadly similar at an intermediate level; and mole rats, which live exclusively underground and tolerate very high levels of CO2.

“Fossorial mammals, such as the mole rat, live exclusively underground in burrows that are both hypoxic and hypercapnic and can thrive under very hypercapnic conditions,” the researchers said.

“We have therefore compared the CO2 sensitivity of Cx26 from human, chicken, rat and mole rat (Heterocephalus glaber).”

They found that the CO2 binding properties matched the sensitivities of these different animals.

Evolutionary natural selection has thus modified the CO2-binding properties of Cx26 – showing that this molecule is a universally important sensor of CO2 in warm blooded animals.

“We find that both the affinity and cooperativity of CO2 binding to Cx26 have been subjected to evolutionary adaption in a manner consistent with the homeostatic requirements of these four species,” the authors explained.

“This is analogous to the evolutionary adaptation of hemoglobin to the needs of O2 transport across the animal kingdom and supports the hypothesis that Cx26 is an important and universal CO2 sensor in homeotherms.”

_____

Elizabeth de Wolf et al. 2017. Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO2. Proc. R. Soc. B 284 (1848): 20162723; doi: 10.1098/rspb.2016.2723

About Skype

Check Also

, Honey Consumption, #Bizwhiznetwork.com Innovation ΛI

Honey Consumption

Honey, especially robinia (also known as acacia honey, a honey from false acacia or black …

Leave a Reply

Your email address will not be published. Required fields are marked *

Bizwhiznetwork Consultation