Sodium channel toxin-resistance mutations do not govern batrachotoxin (BTX) autoresistance in poison birds and frogs

AbstractPoisonous organisms carry small molecule toxins that alter voltage-gated sodium channel (Na✓) function. Among these, batrachotoxin (BTX) from Pitohui toxic 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→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 that compromises channel function, and fails to produce BTX-resistant channels when tested in the context of poison frog Navs. We further show that captive-raised poison frogs are BTX resistant, even though they bear BTX-sensitive Navs. Hence, our data refute the hypothesis that BTX autoresistance is rooted in Nav mutations and instead suggest that more generalizable mechanisms such as toxin sequestration act to protect BTX-bearing species from autointoxication.

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Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on “toxin sponge” proteins

The Journal of General Physiology ◽

10.1085/jgp.202112872 ◽

2021 ◽

Vol 153 (9) ◽

Author(s):

Fayal Abderemane-Ali ◽

Nathan D. Rossen ◽

Megan E. Kobiela ◽

Robert A. Craig ◽

Catherine E. Garrison ◽

...

Keyword(s):

Ion Channel ◽

Sodium Channel ◽

Small Molecule ◽

Resistance Mechanism ◽

Poison Frog ◽

Poison Frogs ◽

Toxin Resistance ◽

Voltage Gated ◽

Primary Driver ◽

Toxin Sequestration

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.

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IDENTIFICATION OF THE kdr MUTATIONS IN VGSC GENE OF THE DENGUE MOSQUITOES AEDES ALBOPICTUS COLLECTED FROM HANOI AND HAIPHONG

Vietnam Journal of Biotechnology ◽

10.15625/1811-4989/16/2/13437 ◽

2018 ◽

Vol 16 (2) ◽

pp. 273-278

Author(s):

Nguyen Thi Kim Lien ◽

Nguyen Thu Hien ◽

Nguyen Huy Hoang ◽

Nguyen Thi Hong Ngoc ◽

Nguyen Thi Huong Binh

Keyword(s):

Sodium Channel ◽

Aedes Albopictus ◽

Novel Mutation ◽

Resistance Mechanism ◽

Resistance Mechanisms ◽

Resistance Mutations ◽

Well Control ◽

Voltage Gated ◽

Activity Of Enzymes ◽

Dengue Epidemic

Vietnam is one of the countries that is affected by dengue fever in Southeast Asia. The dengue epidemic is becoming increasingly more complex so it is necessary to have a well control to vectors in order to limit the spread of the disease. The Aedes albopictus mosquito is determined as one of the two major vectors that transmitted the dengue. Recent research shows that A. albopictus is present in some parts of Hanoi and Haiphong. In order to control the vector as well as the disease, it is necessary to understand the level of resistance and the resistance mechanism of the vector. Two important resistance mechanisms of insect were known as the mutations in the target protein of the insecticides and enhancing the activity of enzymes that participate in the resolution of the insecticides. In this study, the mosquito samples were collected from Hanoi and Haiphong to identify the level of resistance and detect the knock down resistance mutations in voltage gated sodium channel (VGSC) in membrane of nervecell of mosquito. The results of insecticide susceptibility test showed that A. albopictus in Hanoi and Haiphong were still sensitive to organophosphate but resistant to DDT, carbamate and pyrethroid. Ser989Pro, Ile1011Met, Val1016Gly and Phe1534Cys mutations were not deteced in A. albopictus in Hanoi and Haiphong. However, we detected a novel mutation Tyr986His in VGSC protein.

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