Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider
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 afte...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2022-02, Vol.119 (5), p.1-12 |
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| creator | 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. |
| description | 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. |
| doi_str_mv | 10.1073/pnas.2110932119 |
| format | Article |
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B. ; Cristofori-Armstrong, Ben ; Hill, Adam P. ; Herzig, Volker ; King, Glenn F. ; Vetter, Irina ; Rash, Lachlan D. ; Adams, David J. ; Alewood, Paul F.</creator><creatorcontrib>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.</creatorcontrib><description>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.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.2110932119</identifier><identifier>PMID: 35074873</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Action potential ; Action Potentials - drug effects ; Animals ; Baboons ; Biological Sciences ; Coloration ; Dorsal root ganglia ; Ecological adaptation ; Ganglia, Spinal - drug effects ; Hyperalgesia - drug therapy ; Insect bites ; Ion channels ; Ion Channels - metabolism ; Mice ; Muscles ; Nociceptors - drug effects ; Pain ; Pain - drug therapy ; Pain perception ; Papio - metabolism ; Peptides ; Peptides - pharmacology ; Potassium channels (voltage-gated) ; Sodium channels (voltage-gated) ; Spider Venoms - pharmacology ; Spiders ; Spiders - metabolism ; Tetrodotoxin ; Tetrodotoxin - pharmacology ; Venom</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2022-02, Vol.119 (5), p.1-12</ispartof><rights>Copyright © 2022 the Author(s). Published by PNAS.</rights><rights>Copyright National Academy of Sciences Feb 1, 2022</rights><rights>info:eu-repo/semantics/openAccess</rights><rights>Copyright © 2022 the Author(s). Published by PNAS. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-eabfa9e38d251a3c835787c842dcaf61c02b62175bf0d5072a9d69d2821689df3</citedby><cites>FETCH-LOGICAL-c468t-eabfa9e38d251a3c835787c842dcaf61c02b62175bf0d5072a9d69d2821689df3</cites><orcidid>0000-0002-6403-1282 ; 0000-0002-7447-1310 ; 0000-0002-7030-2288 ; 0000-0002-2343-9839 ; 0000-0003-3616-0279 ; 0000-0001-7454-6522 ; 0000-0002-2546-7913 ; 0000-0002-6841-4176 ; 0000-0002-3594-9588 ; 0000-0001-9401-1744 ; 0000-0003-3351-9514 ; 0000-0002-3367-6897 ; 0000-0003-0235-2029 ; 0000-0001-8961-7194 ; 0000-0003-2514-3983 ; 0000-0002-2308-2200 ; 0000-0003-2157-4532</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812547/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8812547/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,26546,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35074873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Finol-Urdaneta, Rocio K.</creatorcontrib><creatorcontrib>Ziegman, Rebekah</creatorcontrib><creatorcontrib>Dekan, Zoltan</creatorcontrib><creatorcontrib>McArthur, Jeffrey R.</creatorcontrib><creatorcontrib>Heitmann, Stewart</creatorcontrib><creatorcontrib>Luna-Ramirez, Karen</creatorcontrib><creatorcontrib>Tae, Han-Shen</creatorcontrib><creatorcontrib>Mueller, Alexander</creatorcontrib><creatorcontrib>Starobova, Hana</creatorcontrib><creatorcontrib>Chin, Yanni K.-Y.</creatorcontrib><creatorcontrib>Wingerd, Joshua S.</creatorcontrib><creatorcontrib>Undheim, Eivind A. B.</creatorcontrib><creatorcontrib>Cristofori-Armstrong, Ben</creatorcontrib><creatorcontrib>Hill, Adam P.</creatorcontrib><creatorcontrib>Herzig, Volker</creatorcontrib><creatorcontrib>King, Glenn F.</creatorcontrib><creatorcontrib>Vetter, Irina</creatorcontrib><creatorcontrib>Rash, Lachlan D.</creatorcontrib><creatorcontrib>Adams, David J.</creatorcontrib><creatorcontrib>Alewood, Paul F.</creatorcontrib><title>Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>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. 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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. 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| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2022-02, Vol.119 (5), p.1-12 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8812547 |
| source | MEDLINE; NORA - Norwegian Open Research Archives; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Action potential Action Potentials - drug effects Animals Baboons Biological Sciences Coloration Dorsal root ganglia Ecological adaptation Ganglia, Spinal - drug effects Hyperalgesia - drug therapy Insect bites Ion channels Ion Channels - metabolism Mice Muscles Nociceptors - drug effects Pain Pain - drug therapy Pain perception Papio - metabolism Peptides Peptides - pharmacology Potassium channels (voltage-gated) Sodium channels (voltage-gated) Spider Venoms - pharmacology Spiders Spiders - metabolism Tetrodotoxin Tetrodotoxin - pharmacology Venom |
| title | Multitarget nociceptor sensitization by a promiscuous peptide from the venom of the King Baboon spider |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T07%3A17%3A23IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multitarget%20nociceptor%20sensitization%20by%20a%20promiscuous%20peptide%20from%20the%20venom%20of%20the%20King%20Baboon%20spider&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Finol-Urdaneta,%20Rocio%20K.&rft.date=2022-02-01&rft.volume=119&rft.issue=5&rft.spage=1&rft.epage=12&rft.pages=1-12&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.2110932119&rft_dat=%3Cjstor_pubme%3E27117762%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2627858339&rft_id=info:pmid/35074873&rft_jstor_id=27117762&rfr_iscdi=true |