TMEM120A/TACAN inhibits mechanically activated PIEZO2 channels

Area of Science:

• Neuroscience
• Molecular Biology
• Ion Channel Physiology

Background:

• PIEZO2 channels are essential for mechanosensation, mediating light touch and proprioception in dorsal root ganglia (DRG) neurons.
• The regulatory proteins controlling PIEZO2 channel activity remain largely uncharacterized.
• TMEM120A (TACAN) was previously hypothesized to be a high-threshold mechanosensitive channel in DRG neurons.

Purpose of the Study:

• To investigate the role of TMEM120A in regulating PIEZO2 channel function.
• To determine if TMEM120A itself possesses mechanosensitive channel activity.
• To elucidate the cellular context of TMEM120A and PIEZO2 interactions.

Main Methods:

• Co-expression of Tmem120a and Piezo2 in a cellular context.
• Electrophysiological recordings to measure mechanically activated currents.
• Utilizing siRNA to knock down Tmem120a expression in mouse DRG neurons.
• Assessing the effects of TMEM120A on PIEZO1 and TREK1 channels.

Main Results:

• Co-expression of Tmem120a with Piezo2 reduced PIEZO2 current amplitudes and elevated activation thresholds.
• TMEM120A did not affect PIEZO1 or TREK1 channel activity.
• TMEM120A alone did not generate detectable mechanosensitive currents.
• Knockdown of Tmem120a in DRG neurons enhanced PIEZO2-mediated currents and lowered activation thresholds.

Conclusions:

• TMEM120A acts as a negative modulator of PIEZO2 channel activity.
• The findings do not support TMEM120A functioning as an independent mechanosensitive ion channel.
• TMEM120A's role is primarily regulatory, specifically impacting PIEZO2 function in sensory neurons.