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

Finol-Urdaneta, Rocio K. and Ziegman, Rebekah and Dekan, Zoltan and McArthur, Jeffrey R. and Heitmann, Stewart and Luna-Ramirez, Karen and Tae, Han-Shen and Mueller, Alexander and Starobova, Hana and Chin, Yanni K.-Y. and Wingerd, Joshua S. and Undheim, Eivind A. B. and Cristofori-Armstrong, Ben and Hill, Adam P. and Herzig, Volker and King, Glenn F. and Vetter, Irina and Rash, Lachlan D. and Adams, David J. and Alewood, Paul F. (2022) Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider. Proceedings of the National Academy of Sciences, 119 (5). ISSN 0027-8424

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Link to published document: http://doi.org/10.1073/pnas.2110932119

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, delta/kappa-theraphotoxin-Pm1a (delta/kappa-TRTX-Pm1a), that elicited nocifensive behavior when injected into mice. In small dorsal root ganglion neurons, synthetic delta/kappa-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 delta/kappa-TRTX-Pm1a may be an evolutionary adaptation in pain-inducing defensive venoms.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 14 Apr 2022 03:21
Last Modified: 14 Apr 2022 03:21
URI: http://eprints.victorchang.edu.au/id/eprint/1202

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