Key Laboratory of Animal Models and Human Disease Mechanisms, Key Laboratory of Bioactive Peptides of Yunnan Province, Engineering Laboratory of Bioactive Peptides, The National & Local Joint Engineering Center of Natural Bioactive Peptides, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650107 Yunnan, China; College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.
College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.
Curr Biol. 2022 Aug 22;32(16):3556-3563.e3. doi: 10.1016/j.cub.2022.06.074. Epub 2022 Jul 20.
Venomous animals utilize venom glands to secrete and store powerful toxins for intraspecific and/or interspecific antagonistic interactions, implying that tissue-specific resistance is essential for venom glands to anatomically separate toxins from other tissues. Here, we show the mechanism of tissue-specific resistance in centipedes (Scolopendra subspinipes mutilans), where the splice variant of the receptor repels its own toxin. Unlike the well-known resistance mechanism by mutation in a given exon, we found that the KCNQ1 channel is highly expressed in the venom gland as a unique splice variant in which the pore domain and transmembrane domain six, partially encoded by exon 6 (rather than 7 as found in other tissues), contain eleven mutated residues. Such a splice variant is sufficient to gain resistance to SsTx (a lethal toxin for giant prey capture) in the venom gland due to a partially buried binding site. Therefore, the tissue-specific KCNQ1 modification confers resistance to the toxins, establishing a safe zone in the venom-storing/secreting environment.
有毒动物利用毒腺分泌和储存强大的毒素，用于种内和/或种间的对抗性相互作用，这意味着组织特异性抗性对于毒腺将毒素与其他组织在解剖上分离至关重要。在这里，我们展示了蜈蚣（Scolopendra subspinipes mutilans）中组织特异性抗性的机制，其中受体的剪接变体排斥其自身的毒素。与已知的通过特定外显子突变的抗性机制不同，我们发现 KCNQ1 通道在毒腺中高度表达，作为一种独特的剪接变体，其孔域和跨膜域六部分由外显子 6（而不是在其他组织中发现的 7）编码，包含十一个突变残基。由于结合位点部分被掩埋，这种剪接变体足以使毒腺获得对 SsTx（一种用于捕获大型猎物的致死毒素）的抗性。因此，组织特异性 KCNQ1 修饰赋予了对毒素的抗性，在储存/分泌毒素的环境中建立了一个安全区。
