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8.A.113.  The Tentonin or TMEM150 (TMEM150) Family 

Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors. These mechanoreceptors involve transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with slow inactivation kinetics exist.  TMEM150c has been reported to either be a channel protein or a Piezo channel protein modifiier. Hong et al. 2016 reported that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with 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, and 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 (Hong et al. 2016). Dubin et al. 2017 showed that if Piezo1 was deleted in mice, no such current was observed.  However, Hong et al. 2017 concluded that TTN3 is a channel protein, but Anderson et al. 2018 reported functional interaction of TMEM150C with mechano-gated ion channels from different classes (Piezo2, Piezo1, and the potassium channel TREK-1).  TMEM150C significantly prolongs the duration of the mechano-current produced by all three channels, decreases the apparent activation threshold in Piezo2, and induces persistent current in Piezo1. They also showed that TMEM150C is co-expressed with Piezo2 in trigeminal neurons, expanding its role beyond proprioceptors (Anderson et al. 2018). It should be noted that this controversy in not yet resolved. For example, Ojeda-Alonso et al. 2022 could not demonstrate channel activity for TMEM150.

References associated with 8.A.113 family:

Anderson, E.O., E.R. Schneider, J.D. Matson, E.O. Gracheva, and S.N. Bagriantsev. (2018). TMEM150C/Tentonin3 Is a Regulator of Mechano-gated Ion Channels. Cell Rep 23: 701-708. 29669276
Chung, J., F. Nakatsu, J.M. Baskin, and P. De Camilli. (2015). Plasticity of PI4KIIIα interactions at the plasma membrane. EMBO Rep 16: 312-320. 25608530
Dubin, A.E., S. Murthy, A.H. Lewis, L. Brosse, S.M. Cahalan, J. Grandl, B. Coste, and A. Patapoutian. (2017). Endogenous Piezo1 Can Confound Mechanically Activated Channel Identification and Characterization. Neuron. 94: 266-270.e3. 28426961
El-Asrag, M.E., P.I. Sergouniotis, M. McKibbin, V. Plagnol, E. Sheridan, N. Waseem, Z. Abdelhamed, D. McKeefry, K. Van Schil, J.A. Poulter, , C.A. Johnson, I.M. Carr, B.P. Leroy, E. De Baere, C.F. Inglehearn, A.R. Webster, C. Toomes, and M. Ali. (2015). Biallelic mutations in the autophagy regulator DRAM2 cause retinal dystrophy with early macular involvement. Am J Hum Genet 96: 948-954. 25983245
Hong, G.S., B. Lee, and U. Oh. (2017). Evidence for Mechanosensitive Channel Activity of Tentonin 3/TMEM150C. Neuron. 94: 271-273.e2. 28426962
Hong, G.S., B. Lee, J. Wee, H. Chun, H. Kim, J. Jung, J.Y. Cha, T.R. Riew, G.H. Kim, I.B. Kim, and U. Oh. (2016). Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neuron.s with Proprioceptive Function. Neuron. 91: 107-118. 27321926
Mrschtik, M., J. O''Prey, L.Y. Lao, J.S. Long, F. Beaumatin, D. Strachan, M. O''Prey, J. Skommer, and K.M. Ryan. (2015). DRAM-3 modulates autophagy and promotes cell survival in the absence of glucose. Cell Death Differ 22: 1714-1726. 25929859
Ojeda-Alonso, J., V. Bégay, J.A. Garcia-Contreras, A.F. Campos-Pérez, B. Purfürst, and G.R. Lewin. (2022). Lack of evidence for participation of TMEM150C in sensory mechanotransduction. J Gen Physiol 154:. 36256908
Park, S.M., K. Kim, E.J. Lee, B.K. Kim, T.J. Lee, T. Seo, I.S. Jang, S.H. Lee, S. Kim, J.H. Lee, and J. Park. (2009). Reduced expression of DRAM2/TMEM77 in tumor cells interferes with cell death. Biochem. Biophys. Res. Commun. 390: 1340-1344. 19895784
Wei, M., Z. Zhu, J. Wu, Y. Wang, J. Geng, and Z.H. Qin. (2019). DRAM1 deficiency affects the organization and function of the Golgi apparatus. Cell Signal 63: 109375. [Epub: Ahead of Print] 31356858