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 completely resolved.



This family belongs to the .

 

References:

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.

Chung, J., F. Nakatsu, J.M. Baskin, and P. De Camilli. (2015). Plasticity of PI4KIII╬▒ interactions at the plasma membrane. EMBO Rep 16: 312-320.

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.

Hong, G.S., B. Lee, and U. Oh. (2017). Evidence for Mechanosensitive Channel Activity of Tentonin 3/TMEM150C. Neuron. 94: 271-273.e2.

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.

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.

Examples:

TC#NameOrganismal TypeExample
8.A.113.1.1

TMEM150c/Tentonin 3 of 249 aas and 6 TMSs.  According to Anderson et al. 2018, it reglulates other channels such as Piezo 1 and Piezo 2. According to Hong et al. 2017, it has inherent channel activity.

TMEM150c of Homo sapiens

 
8.A.113.1.2

TMEM150a of 271 aas and 6 TMSs.  Regulates localization of phosphatidylinositol 4-kinase (PI4K) to the plasma membrane (Chung et al. 2015). Acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns4P) synthesis (Chung et al. 2015). May also play a role in fasting-induced catabolism.

TMEM150a of Homo sapiens

 
8.A.113.1.3

TMEM150b of 233 aas and 6 TMSs.  Modulator of macroautophagy that causes accumulation of autophagosomes under basal conditions and enhances autophagic flux. Represses cell death and promotes long-term clonogenic survival of cells grown in the absence of glucose in a macroautophagy-independent manner (Mrschtik et al. 2015). May have some role in extracellular matrix engulfment or growth factor receptor recycling, both of which can modulate cell survival.

TMEM150b of Homo sapiens

 
8.A.113.1.4

Uncharacterized TMEM150 homologue of 252 aas and 6 TMSs.

UP of Schistosoma japonicum (Blood fluke)

 
8.A.113.1.5

Uncharacterized DNA damage-regulated autophagy modulator protein 2 of 243 aas and 6 TMSs.

UP of Anoplophora glabripennis (Asian longhorned beetle)

 
8.A.113.1.6

Uncharacterized TMEM150b-like protein of 251 aas and 6 TMSs.

UP of Branchiostoma belcheri (Belcher's lancelet) Isolated from sea water.

 
8.A.113.1.7

Uncharacterized protein of 268 aas and 6 TMSs.

UP of Pristionchus pacificus (Parasitic nematode)