Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on 'toxin sponge' proteins
| العنوان: | Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on 'toxin sponge' proteins |
|---|---|
| المؤلفون: | Claire M. Colleran, Robert A. Craig, Catherine E. Garrison, Megan E. Kobiela, Zhou Chen, John P. Dumbacher, Lauren A. O’Connell, Fayal Abderemane-Ali, Daniel L. Minor, Nathan D. Rossen, J. Du Bois |
| المصدر: | The Journal of general physiology, vol 153, iss 9 The Journal of General Physiology |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Amphibian, Phyllobates, Molecular Pharmacology, Physiology, Medical Physiology, Biophysics, medicine.disease_cause, complex mixtures, Article, Poisons, Sodium Channels, Molecular Physiology, Birds, chemistry.chemical_compound, biology.animal, medicine, Animals, Batrachotoxins, Genetics, Saxitoxin, Mutation, biology, Toxin, Sodium channel, biology.organism_classification, chemistry, Pitohui, Batrachotoxin, Anura |
| الوصف: | Some poisonous animals produce toxins that affect Na+ channel function yet avoid autointoxication. Abderemane-Ali et al. show that resistance by Pitohui birds and Phyllobates frogs to their own toxins may be mediated not by mutations in their channels, but by toxin-sequestering “sponge” proteins. Many poisonous organisms carry small-molecule toxins that alter voltage-gated sodium channel (NaV) function. Among these, batrachotoxin (BTX) from Pitohui poison birds and Phyllobates poison frogs stands out because of its lethality and unusual effects on NaV function. How these toxin-bearing organisms avoid autointoxication remains poorly understood. In poison frogs, a NaV DIVS6 pore-forming helix N-to-T mutation has been proposed as the BTX resistance mechanism. Here, we show that this variant is absent from Pitohui and poison frog NaVs, incurs a strong cost compromising channel function, and fails to produce BTX-resistant channels in poison frog NaVs. We also show that captivity-raised poison frogs are resistant to two NaV-directed toxins, BTX and saxitoxin (STX), even though they bear NaVs sensitive to both. Moreover, we demonstrate that the amphibian STX “toxin sponge” protein saxiphilin is able to protect and rescue NaVs from block by STX. Taken together, our data contradict the hypothesis that BTX autoresistance is rooted in the DIVS6 N→T mutation, challenge the idea that ion channel mutations are a primary driver of toxin resistance, and suggest the possibility that toxin sequestration mechanisms may be key for protecting poisonous species from the action of small-molecule toxins. |
| وصف الملف: | application/pdf |
| تدمد: | 1540-7748 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0c8851458c1711bcba644a3cefa40512 https://pubmed.ncbi.nlm.nih.gov/34491263 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....0c8851458c1711bcba644a3cefa40512 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15407748 |
|---|