Sodium Channel Subunits-An Additional Element in Animal Tetrodotoxin Resistance?

International Journal of Molecular Sciences(2024)

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摘要
Tetrodotoxin (TTX) is a neurotoxic molecule used by many animals for defense and/or predation, as well as an important biomedical tool. Its ubiquity as a defensive agent has led to repeated independent evolution of tetrodotoxin resistance in animals. TTX binds to voltage-gated sodium channels (VGSC) consisting of alpha and beta subunits. Virtually all studies investigating the mechanisms behind TTX resistance have focused on the alpha subunit of voltage-gated sodium channels, where tetrodotoxin binds. However, the possibility of beta subunits also contributing to tetrodotoxin resistance was never explored, though these subunits act in concert. In this study, we present preliminary evidence suggesting a potential role of beta subunits in the evolution of TTX resistance. We gathered mRNA sequences for all beta subunit types found in vertebrates across 12 species (three TTX-resistant and nine TTX-sensitive) and tested for signatures of positive selection with a maximum likelihood approach. Our results revealed several sites experiencing positive selection in TTX-resistant taxa, though none were exclusive to those species in subunit beta 1, which forms a complex with the main physiological target of TTX (VGSC Na(v)1.4). While experimental data validating these findings would be necessary, this work suggests that deeper investigation into beta subunits as potential players in tetrodotoxin resistance may be worthwhile.
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关键词
tetrodotoxin,resistance,sodium channels,subunit beta
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