Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider

Rocio K Finol-Urdaneta; Rebekah Ziegman; Zoltan Dekan; Jeffrey R McArthur; Stewart Heitmann; Karen Luna-Ramirez; Han-Shen Tae; Alexander Mueller; Hana Starobova; Yanni K-Y Chin; Joshua S Wingerd; Eivind A B Undheim; Ben Cristofori-Armstrong; Adam P Hill; Volker Herzig; Glenn F King; Irina Vetter; Lachlan D Rash; David J Adams; Paul F Alewood

doi:10.1073/pnas.2110932119

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Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider

Journal article

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Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider

Rocio K Finol-Urdaneta, Rebekah Ziegman, Zoltan Dekan, Jeffrey R McArthur, Stewart Heitmann, Karen Luna-Ramirez, Han-Shen Tae, Alexander Mueller, Hana Starobova, Yanni K-Y Chin, …

National Academy of Sciences. Proceedings, Vol.119(5), pp.1-12

2022

DOI: https://doi.org/10.1073/pnas.2110932119

PMID: 35074873

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Abstract

Pain

NaV1.8

KV2.1

hyperexcitability

target promiscuity

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.

Details

Title: Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider
Authors: Rocio K Finol-Urdaneta (Corresponding Author) - University of Wollongong
Rebekah Ziegman (Author) - The University of Queensland
Zoltan Dekan (Author) - The University of Queensland
Jeffrey R McArthur (Author) - University of Wollongong
Stewart Heitmann (Author) - Victor Chang Cardiac Research Institute
Karen Luna-Ramirez (Author) - University of Wollongong
Han-Shen Tae (Author) - University of Wollongong
Alexander Mueller (Author) - The University of Queensland
Hana Starobova (Author) - The University of Queensland
Yanni K-Y Chin (Author) - The University of Queensland
Joshua S Wingerd (Author) - Institute for Molecular Bioscience, University of Queensland, St. Lucia, QLD 4072, Australia
Eivind A B Undheim (Author) - The University of Queensland
Ben Cristofori-Armstrong (Author) - The University of Queensland
Adam P Hill (Author) - UNSW Australia
Volker Herzig (Author) - University of the Sunshine Coast, Queensland, School of Science, Technology and Engineering
Glenn F King (Author) - The University of Queensland
Irina Vetter (Author) - CSIRO Agriculture and Food (Australia)
Lachlan D Rash (Author) - School of Biomedical Sciences, University of Queensland, St. Lucia, QLD 4072, Australia
David J Adams (Corresponding Author) - University of Wollongong
Paul F Alewood (Corresponding Author) - The University of Queensland
Publication details: National Academy of Sciences. Proceedings, Vol.119(5), pp.1-12
Publisher: National Academy of Sciences
Date published: 2022
DOI: 10.1073/pnas.2110932119
ISSN: 1091-6490; 0027-8424
PMID: 35074873
Copyright note: This article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
Grants: Discovery and development of better pain treatments, 1072113, National Health and Medical Research Council (Australia, Canberra) - NHMRC
ARC Centre of Excellence for Innovations in Peptide and Protein Science, CE200100012 , Australian Research Council (Australia, Canberra) - ARC
Venoms to drugs: translating venom peptides into human therapeutics, 1136889, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Developing subtype-selective blockers of acid-sensing ion channels for treating peripheral pain, 1067940, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Accessing structurally elusive states of sodium channels as novel analgesic targets, 1162597, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Unravelling the structural evolution of centipede toxins, DE160101142 , Australian Research Council (Australia, Canberra) - ARC
Grant note: Research Council of Norway FRIPRO-YRT Fellowship 287462 (to E.A.B.U.); and Rebecca Cooper Foundation for Medical Research Grant PG2019396 (to J.R.M.). A.M. was supported by an Australian Government Research Training Program Scholarship.
Organisation Unit: University of the Sunshine Coast, Queensland; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99603408102621
Output Type: Journal article

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