Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on "toxin sponge" proteins.
Evidence that toxin resistance in poison birds and frogs is not rooted in sodium channel mutations and may rely on "toxin sponge" proteins.
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DOI：
10.1085/jgp.202112872
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发表时间：
2021-09-06
期刊：
影响因子：
--
通讯作者：
Minor DL
中科院分区：
文献类型：
--
作者：
Abderemane-Ali F;Rossen ND;Kobiela ME;Craig RA;Garrison CE;Chen Z;Colleran CM;O'Connell LA;Du Bois J;Dumbacher JP;Minor DL
一些有毒动物产生影响Na+通道功能的毒素，但避免自中毒。Abderemane-Ali等人表明，Pitohui鸟和叶叶蛙对自身毒素的抗性可能不是由通道突变介导的，而是由毒素隔离的“海绵”蛋白介导的。许多有毒生物携带的小分子毒素会改变电压门控钠通道（NaV）的功能。其中，来自Pitohui毒鸟和叶叶毒蛙的batrachotoxin （BTX）因其致死性和对NaV功能的不同寻常的影响而引人注目。这些携带毒素的生物体如何避免自身中毒仍然知之甚少。在毒蛙中，NaV DIVS6成孔螺旋N-to-T突变被认为是BTX抗性的机制。在这里，我们发现这种变异在Pitohui和毒蛙的nav中不存在，导致了强烈的成本妥协通道功能，并且在毒蛙的nav中不能产生抗btx的通道。我们还发现，圈养的毒蛙对两种nav导向的毒素，BTX和石笋毒素（STX）有抗性，尽管它们对这两种毒素都敏感。此外，我们证明了两栖动物STX“毒素海绵”蛋白saxiphilin能够保护和拯救被STX阻断的nav。综上所述，我们的数据反驳了BTX自身抗性源于DIVS6 N→T突变的假设，挑战了离子通道突变是毒素抗性主要驱动因素的观点，并表明毒素隔离机制可能是保护有毒物种免受小分子毒素作用的关键。
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.
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影响因子：
2.3
作者：
DALY, JW;GARRAFFO, HM;RAND, AS
通讯作者：
RAND, AS
影响因子：
4.5
作者：
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通讯作者：
HORN, R
影响因子：
2.3
作者：
Daly, John W.;Garraffo, H. Martin;Vences, Miguel
通讯作者：
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影响因子：
1.7
作者：
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通讯作者：
Pevzner, Pavel A.
DOI：
10.1073/pnas.212638099
发表时间：
2002-12-24
影响因子：
11.1
作者：
Chen, CL;Bharucha, V;Isom, LL
通讯作者：
Isom, LL