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  2. Venom resistance mechanisms in centipede show tissue specificity

Venom resistance mechanisms in centipede show tissue specificity

  • Curr Biol. 2022 Aug 22;32(16):3556-3563.e3. doi: 10.1016/j.cub.2022.06.074.
Yunfei Wang 1 Chuanlin Yin 2 Hao Zhang 3 Peter Muiruri Kamau 3 Wenqi Dong 2 Anna Luo 3 Longhui Chai 2 Shilong Yang 4 Ren Lai 5
Affiliations

Affiliations

  • 1 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.
  • 2 College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China.
  • 3 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 4 College of Wildlife and Protected Area, Northeast Forestry University, Harbin 150040, China. Electronic address: syang2020@nefu.edu.cn.
  • 5 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; Kunming College of Life Science, University of Chinese Academy of Sciences, Beijing 100049, China; Sino-African Joint Research Center, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China. Electronic address: rlai@mail.kiz.ac.cn.
Abstract

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.

Keywords

KCNQ1; SsTx; centipede; ion channel; resistance; splice variant; tissue specificity; toxin; venom gland.

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