Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neurons with Proprioceptive Function.
Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c markedly reduced slowly adapting neurons in dorsal-root ganglion neurons. The MA TTN3 currents were inhibited by known blockers of mechanosensitive ion channels. Moreover, TTN3 was localized in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of coordinated movements and abnormal gait. Thus, TTN3 appears to be a component of a mechanosensitive channel with a slow inactivation rate and contributes to motor coordination. Identification of this gene advances our understanding of the various types of mechanosensations, including proprioception.
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Gyunggy 16229, Korea.
Gyu-Sang
GS
Hong
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Gyunggy 16229, Korea.
Byeongjun
B
Lee
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Gyunggy 16229, Korea.
Jungwon
J
Wee
Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Hyeyeon
H
Chun
Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Hyungsup
H
Kim
Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Jooyoung
J
Jung
Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 08826, Korea.
Joo Young
JY
Cha
Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, Catholic University, Seoul 06591, Korea.
Tae-Ryong
TR
Riew
Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, Catholic University, Seoul 06591, Korea.
Gyu Hyun
GH
Kim
Department of Anatomy, Catholic Neuroscience Institute, College of Medicine, Catholic University, Seoul 06591, Korea.
In-Beom
IB
Kim
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Gyunggy 16229, Korea; Sensory Research Center, CRI, College of Pharmacy, Seoul National University, Seoul 08826, Korea. Electronic address: utoh@snu.ac.kr.
Uhtaek
U
Oh
D000818:Animals; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000378:metabolism*; D008465:Mechanoreceptors / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism*; D014110:Touch / Q000502:physiology
D007473:Ion Channels; D008565:Membrane Proteins; C000621720:TTN3 protein, mouse