Pain-causing stinging nettle toxins target TMEM233 to modulate Na_V1.7 function.

ABSTRACT: Voltage-gated sodium (Na_V) channels are critical regulators of neuronal excitability and are targeted by many toxins that directly interact with the pore-forming α subunit, typically via extracellular loops of the voltage-sensing domains, or residues forming part of the pore domain. Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na_V channel modulating peptide toxin. Here we show that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for pharmacological activity of ExTxA at Na_V channels, and that co-expression of TMEM233 modulates the gating properties of Na_V1.7. These findings identify TMEM

SUBMITTER: Jami S 

PROVIDER: S-EPMC10147923 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature