Document of bibliographic reference 301544
BibliographicReference record
- Type
- Bibliographic resource
- Type of document
- Journal article
- BibLvlCode
- AS
- Title
- Novel analgesic ω-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides
- Abstract
- Cone snails are a diverse group of predatory marine invertebrates that deploy remarkably complex venoms to rapidly paralyse worm, mollusc or fish prey. ω-Conotoxins are neurotoxic peptides from cone snail venoms that inhibit Cav2.2 voltage-gated calcium channel, demonstrating potential for pain management via intrathecal (IT) administration. Here, we isolated and characterized two novel ω-conotoxins, MoVIA and MoVIB from Conus moncuri, the first to be identified in vermivorous (worm-hunting) cone snails. MoVIA and MoVIB potently inhibited human Cav2.2 in fluorimetric assays and rat Cav2.2 in patch clamp studies, and both potently displaced radiolabeled ω-conotoxin GVIA (125I-GVIA) from human SH-SY5Y cells and fish brain membranes (IC50 2–9 pM). Intriguingly, an arginine at position 13 in MoVIA and MoVIB replaced the functionally critical tyrosine found in piscivorous ω-conotoxins. To investigate its role, we synthesized MoVIB-[R13Y] and MVIIA-[Y13R]. Interestingly, MVIIA-[Y13R] completely lost Cav2.2 activity and MoVIB-[R13Y] had reduced activity, indicating that Arg at position 13 was preferred in these vermivorous ω-conotoxins whereas tyrosine 13 is preferred in piscivorous ω-conotoxins. MoVIB reversed pain behavior in a rat neuropathic pain model, confirming that vermivorous cone snails are a new source of analgesic ω-conotoxins. Given vermivorous cone snails are ancestral to piscivorous species, our findings support the repurposing of defensive venom peptides in the evolution of piscivorous Conidae.
- WebOfScience code
- https://www.webofscience.com/wos/woscc/full-record/WOS:000444022800001
- Bibliographic citation
- Sousa, S.R.; McArthur, J.R.; Brust, A.; Bhola, R.F.; Rosengren, K.J.; Ragnarsson, L.; Dutertre, S.; Alewood, P.F.; Christie, M.J.; Adams, D.J.; Vetter, I.; Lewis, R.J. (2018). Novel analgesic ω-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides. NPG Scientific Reports 8(1): 15 pp. https://dx.doi.org/10.1038/s41598-018-31245-4
- Is peer reviewed
- true
- Access rights
- open access
- Is accessible for free
- true
Authors
- author
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- Name
- Silmara Sousa
- author
-
- Name
- Jeffrey McArthur
- author
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- Name
- Andreas Brust
- author
-
- Name
- Rebecca Bhola
- author
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- Name
- K. Johan Rosengren
- author
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- Name
- Lotten Ragnarsson
- author
-
- Name
- Sébastien Dutertre
- author
-
- Name
- Paul Alewood
- author
-
- Name
- MacDonald Christie
- author
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- Name
- David Adams
- author
-
- Name
- Irina Vetter
- Identifier
- https://orcid.org/0000-0002-3594-9588
- author
-
- Name
- Richard Lewis