The identity of ion channels involved in sensing mechanical force has remained elusive. Mechanically-activated (MA) cation channels function as touch/pain sensors, and are also required for hearing, adjustment of vascular tone and other functions. Indeed, mechanotransduction is the least understood sensory transduction system at the molecular level. We recently identified MA cation channel components in vertebrates named Piezo1 and Piezo2. Expressing Piezos in a variety of mammalian cell lines induce large MA cationic currents. Furthermore, we show that RNAi against Piezo2 in somatosensory neurons specifically downregulates rapidly-adapting MA cation currents. Here, we test the hypothesis that Piezo2 is required for somatosensory mechanotransduction

Public Health Relevance

TSRI Mechanical sensation is inextricably linked to inflammatory pain states caused by diseases such as Arthritis and Temperomandibular Disorders, where even minimal movement of joints (walking, chewing, and speaking) cause pain and lead to symptoms such as chronic headache and ringing in the ears. Therefore, a molecular understanding of thermal and mechanical sensation is important and relevant to the field of pain.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01DE022358-03
Application #
8685768
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Wan, Jason
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Woo, Seung-Hyun; Lumpkin, Ellen A; Patapoutian, Ardem (2015) Merkel cells and neurons keep in touch. Trends Cell Biol 25:74-81
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
Woo, Seung-Hyun; Ranade, Sanjeev; Weyer, Andy D et al. (2014) Piezo2 is required for Merkel-cell mechanotransduction. Nature 509:622-6
Ranade, Sanjeev S; Qiu, Zhaozhu; Woo, Seung-Hyun et al. (2014) Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc Natl Acad Sci U S A 111:10347-52
Maksimovic, Srdjan; Nakatani, Masashi; Baba, Yoshichika et al. (2014) Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509:617-21