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Publication : TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction.

First Author  Zhang X Year  2024
Journal  Cell Rep Volume  43
Issue  4 Pages  114014
PubMed ID  38568807 Mgi Jnum  J:349398
Mgi Id  MGI:7627910 Doi  10.1016/j.celrep.2024.114014
Citation  Zhang X, et al. (2024) TMC7 functions as a suppressor of Piezo2 in primary sensory neurons blunting peripheral mechanotransduction. Cell Rep 43(4):114014
abstractText  The transmembrane channel-like (TMC) protein family comprises eight members, with TMC1 and TMC2 being extensively studied. This study demonstrates substantial co-expression of TMC7 with the mechanosensitive channel Piezo2 in somatosensory neurons. Genetic deletion of TMC7 in primary sensory ganglia neurons in vivo enhances sensitivity in both physiological and pathological mechanosensory transduction. This deletion leads to an increase in proportion of rapidly adapting (RA) currents conducted by Piezo2 in dorsal root ganglion (DRG) neurons and accelerates RA deactivation kinetics. In HEK293 cells expressing both proteins, TMC7 significantly suppresses the current amplitudes of co-expressed Piezo2. Our findings reveal that TMC7 and Piezo2 exhibit physical interactions, and both proteins also physically interact with cytoskeletal beta-actin. We hypothesize that TMC7 functions as an inhibitory modulator of Piezo2 in DRG neurons, either through direct inhibition or by disrupting the transmission of mechanical forces from the cytoskeleton to the channel.
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