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Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider.
Finol-Urdaneta, Rocio K; Ziegman, Rebekah; Dekan, Zoltan; McArthur, Jeffrey R; Heitmann, Stewart; Luna-Ramirez, Karen; Tae, Han-Shen; Mueller, Alexander; Starobova, Hana; Chin, Yanni K-Y; Wingerd, Joshua S; Undheim, Eivind A B; Cristofori-Armstrong, Ben; Hill, Adam P; Herzig, Volker; King, Glenn F; Vetter, Irina; Rash, Lachlan D; Adams, David J; Alewood, Paul F.
  • Finol-Urdaneta RK; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia; rfinolu@uow.edu.au djadams@uow.edu.au p.alewood@imb.uq.edu.au.
  • Ziegman R; Electrophysiology Facility for Cell Phenotyping and Drug Discovery, Wollongong, NSW 2522, Australia.
  • Dekan Z; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia.
  • McArthur JR; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Heitmann S; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Luna-Ramirez K; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
  • Tae HS; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia.
  • Mueller A; Victor Chang Cardiac Research Institute, Darlinghurst, NSW 2010, Australia.
  • Starobova H; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
  • Chin YK; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia.
  • Wingerd JS; Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, Australia.
  • Undheim EAB; Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia.
  • Cristofori-Armstrong B; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Hill AP; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Herzig V; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • King GF; Centre for Advanced Imaging, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Vetter I; Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Rash LD; Centre for Advanced Imaging, University of Queensland, St. Lucia, QLD 4072, Australia.
  • Adams DJ; Centre for Biodiversity Dynamics, Department of Biology, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
  • Alewood PF; Centre for Ecology and Evolutionary Synthesis, Department of Bioscience, University of Oslo, 0316 Oslo, Norway.
Proc Natl Acad Sci U S A ; 119(5)2022 02 01.
Article en En | MEDLINE | ID: mdl-35074873
ABSTRACT
The King Baboon spider, Pelinobius muticus, is a burrowing African tarantula. Its impressive size and appealing coloration are tempered by reports describing severe localized pain, swelling, itchiness, and muscle cramping after accidental envenomation. Hyperalgesia is the most prominent symptom after bites from P. muticus, but the molecular basis by which the venom induces pain is unknown. Proteotranscriptomic analysis of P. muticus venom uncovered a cysteine-rich peptide, δ/κ-theraphotoxin-Pm1a (δ/κ-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic δ/κ-TRTX-Pm1a (sPm1a) induced hyperexcitability by enhancing tetrodotoxin-resistant sodium currents, impairing repolarization and lowering the threshold of action potential firing, consistent with the severe pain associated with envenomation. The molecular mechanism of nociceptor sensitization by sPm1a involves multimodal actions over several ion channel targets, including NaV1.8, KV2.1, and tetrodotoxin-sensitive NaV channels. The promiscuous targeting of peptides like δ/κ-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Papio / Péptidos / Venenos de Araña / Arañas / Nociceptores Límite: Animals Idioma: En Año: 2022 Tipo del documento: Article
Texto completo
Imprimir
XML
PubMed Links
Search on Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Papio / Péptidos / Venenos de Araña / Arañas / Nociceptores Límite: Animals Idioma: En Año: 2022 Tipo del documento: Article