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Protein monitors lung volume, regulates our breathing
The study, published in Nature, shows how the Piezo2 protein, previously shown to be the principal sensor of touch and proprioception (or sense of the relative position of neighbouring parts of the body), also plays a critical role in sensing lung expansion.
"The discoveries here could provide important clues on how to treat patients with respiratory disorders" said senior author Ardem Patapoutian, a professor at TSRI and a Howard Hughes Medical Institute (HHMI) investigator.
They believe their study helps shed light on sudden infant death syndrome (SIDS) in human babies, which is thought to be associated with dysfunctional airway sensory neurons.
Adult mice without the Piezo2 channel in their sensory neurons, exhibit significantly increased tidal volume (the amount of inhaled air in lungs) as well as an impaired Hering-Breuer reflex, an inhibitory reflex preventing lung over-expansion.
"Previous studies suggested the existence of lung inflation sensors; however, their molecular identity or physiological importance has not been clarified," adds Patapoutian.
Researchers tackled this question by generating Piezo2 "knockout" mice, in which the Piezo2 channel is deleted throughout the animal — or only from sensory neurons (specifically, vagal sensory neurons known to control breathing). They found that Piezo2 is essential for establishing proper breathing and lung expansion in newborn mice. Piezo2-deficient newborn mice showed unexpanded lungs and significantly more shallow breathing.
Strikingly, according to recently published papers, Piezo2-deficient human infants also show shallow breathing and require medical attention.
"Piezo2-deficient newborn mice develop normally until birth. The problem only arise once the mice are born and try to breathe on their own" added Nonomura.
The researchers were surprised to see an unexpected consequence of deleting Piezo2 in sensory neurons of adult mice. When the Piezo2 channel was deleted either in all sensory neurons or only from vagal sensory neurons, adult mice could still breathe, but they inhaled significantly more air than Piezo2-intact mice.
Under normal conditions, animals stop breathing when they are forced to breathe in more air, but Piezo2-deficient adult mice lack the Hering-Breuer reflex and continued breathing when they were forced to breathe in more air.
Why this difference between adults and newborns? Researchers believe that Piezo2 performs different functions in newborns and adults because establishing autonomous breathing in newborns is more complex.
This data, for the first time, defines the importance of mechano-sensory transference of DNA from one bacterium to another — via a virus — in adult respiration. This research is also relevant to our understanding of respiratory diseases as chronic obstructive pulmonary disease (COPD) and sleep apnea appear to be tied to disruption in airway sensory feedback.
The team believes future studies could use similar genetic manipulation to better understand the role of Piezo2 in other physiological processes — such as heart rate control and bladder function.
In addition to Nonomura, Woo and Patapoutian, authors of the study, "Piezo2 senses airway stretch and mediates lung inflation-induced apnoea," were Rui B. Chang and Stephen D. Liberles of Harvard Medical School; Astrid Gillich of HHMI and the Stanford University School of Medicine; Zhaozhu Qiu, previously of TSRI and the Genomics Institute of the Novartis Foundation, now at Johns Hopkins University; Allain G. Francisco of HHMI and TSRI; and Sanjeev S. Ranade, previously of HHMI and TSRI, and now at the Gladstone Institutes.
This research was supported by the National Institutes of Health (grants R01DE022358 and R01HL132255), a Giovanni Armenise-Harvard Foundation Grant and the Howard Hughes Medical Institute.
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Immunofluorescence of PIEZO2 Antibody - Staining of human cell line