Sodium Channel ß Subunits-An Additional Element in Animal Tetrodotoxin Resistance?
Int J Mol Sci
; 25(3)2024 Jan 25.
Article
en En
| MEDLINE
| ID: mdl-38338757
ABSTRACT
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 α and ß subunits. Virtually all studies investigating the mechanisms behind TTX resistance have focused on the α subunit of voltage-gated sodium channels, where tetrodotoxin binds. However, the possibility of ß 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 ß subunits in the evolution of TTX resistance. We gathered mRNA sequences for all ß 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 ß1, which forms a complex with the main physiological target of TTX (VGSC Nav1.4). While experimental data validating these findings would be necessary, this work suggests that deeper investigation into ß subunits as potential players in tetrodotoxin resistance may be worthwhile.
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Base de datos:
MEDLINE
Asunto principal:
Canales de Sodio Activados por Voltaje
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2024
Tipo del documento:
Article
País de afiliación:
Australia