[PDF][PDF] Tentonin 3/TMEM150c confers distinct mechanosensitive currents in dorsal-root ganglion neurons with proprioceptive function

GS Hong, B Lee, J Wee, H Chun, H Kim, J Jung… - Neuron, 2016 - cell.com
GS Hong, B Lee, J Wee, H Chun, H Kim, J Jung, JY Cha, TR Riew, GH Kim, IB Kim, U Oh
Neuron, 2016cell.com
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 …
Summary
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.
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