Respiratory organs experience repetitive and wide-ranging mechanical forces during respiration. These mechanical forces within the airway are thought to serve as cues to trigger physiological responses. Yet, the respiratory function of mechanotransduction is not well established, partly due to our inability to selectively modulate mechanotransduction. We recently reported that Piezo2, a mechanically activated cation channel, is the principal mechanotransducer in low threshold cutaneous mechanoreceptors and skeletal muscle-innervating proprioceptors in mice. Based on its function as a mechanotransducer, its abundance in various populations of sensory neurons, and preliminary data presented here, we will explore the role of mechanotransduction in respiratory function using Piezo-deficient and Piezo-gain-of-function mouse models.

Public Health Relevance

Respiratory dysfunction is a notorious cause of perinatal mortality in infants and of sleep apnea (temporary cessation of breathing) in adults, and yet the mechanisms of respiratory control are not clearly established. Gain of function mutations in mechanically activated Piezo2 ion channels in humans cause arthrogryposis with restrictive lung disease. Here, we will explore the role of Piezo ion channel in respiratory control.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
2R01DE022358-06
Application #
9239453
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Vallejo-Estrada, Yolanda
Project Start
2012-07-12
Project End
2021-08-31
Budget Start
2016-09-21
Budget End
2017-08-31
Support Year
6
Fiscal Year
2016
Total Cost
$481,250
Indirect Cost
$231,250
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
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Ma, Shang; Cahalan, Stuart; LaMonte, Gregory et al. (2018) Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection. Cell 173:443-455.e12
Wu, Zizhen; Grillet, Nicolas; Zhao, Bo et al. (2017) Mechanosensory hair cells express two molecularly distinct mechanotransduction channels. Nat Neurosci 20:24-33
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Ranade, Sanjeev S; Woo, Seung-Hyun; Dubin, Adrienne E et al. (2014) Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516:121-5

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