Embryonic Toxin Expression in the Cone Snail Conus Victoriae: Primed to Kill or Divergent Function?

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2011 Apr 21

PMID 21504902

Citations 14

Authors

Helena Safavi-Hemami

William A Siero

Zhihe Kuang

Nicholas A Williamson

John A Karas

Louise R Page

David Macmillan

Brid Callaghan

Shiva Nag Kompella

David J Adams

Raymond S Norton

Anthony W Purcell

Affiliations

Soon will be listed here.

Abstract

Predatory marine cone snails (genus Conus) utilize complex venoms mainly composed of small peptide toxins that target voltage- and ligand-gated ion channels in their prey. Although the venoms of a number of cone snail species have been intensively profiled and functionally characterized, nothing is known about the initiation of venom expression at an early developmental stage. Here, we report on the expression of venom mRNA in embryos of Conus victoriae and the identification of novel α- and O-conotoxin sequences. Embryonic toxin mRNA expression is initiated well before differentiation of the venom gland, the organ of venom biosynthesis. Structural and functional studies revealed that the embryonic α-conotoxins exhibit the same basic three-dimensional structure as the most abundant adult toxin but significantly differ in their neurological targets. Based on these findings, we postulate that the venom repertoire of cone snails undergoes ontogenetic changes most likely reflecting differences in the biotic interactions of these animals with their prey, predators, or competitors. To our knowledge, this is the first study to show toxin mRNA transcripts in embryos, a finding that extends our understanding of the early onset of venom expression in animals and may suggest alternative functions of peptide toxins during development.

Citing Articles

Coordinated adaptations define the ontogenetic shift from worm- to fish-hunting in a venomous cone snail.

Rogalski A, Himaya S, Lewis R Nat Commun. 2023; 14(1):3287.

PMID: 37311767 PMC: 10264353. DOI: 10.1038/s41467-023-38924-5.

α7- and α9-Containing Nicotinic Acetylcholine Receptors in the Functioning of Immune System and in Pain.

Shelukhina I, Siniavin A, Kasheverov I, Ojomoko L, Tsetlin V, Utkin Y Int J Mol Sci. 2023; 24(7).

PMID: 37047495 PMC: 10095066. DOI: 10.3390/ijms24076524.

Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications.

Kasheverov I, Kudryavtsev D, Shelukhina I, Nikolaev G, Utkin Y, Tsetlin V Biomolecules. 2022; 12(2).

PMID: 35204690 PMC: 8961598. DOI: 10.3390/biom12020189.

Insights into how development and life-history dynamics shape the evolution of venom.

Surm J, Moran Y Evodevo. 2021; 12(1):1.

PMID: 33413660 PMC: 7791878. DOI: 10.1186/s13227-020-00171-w.

Dynamics of venom composition across a complex life cycle.

Columbus-Shenkar Y, Sachkova M, Macrander J, Fridrich A, Modepalli V, Reitzel A Elife. 2018; 7.

PMID: 29424690 PMC: 5832418. DOI: 10.7554/eLife.35014.

References

Lopez-Vera E, Aguilar M, Schiavon E, Marinzi C, Ortiz E, Cassulini R . Novel alpha-conotoxins from Conus spurius and the alpha-conotoxin EI share high-affinity potentiation and low-affinity inhibition of nicotinic acetylcholine receptors. FEBS J. 2007; 274(15):3972-85. DOI: 10.1111/j.1742-4658.2007.05931.x. View

Loughnan M, Nicke A, Jones A, Adams D, Alewood P, Lewis R . Chemical and functional identification and characterization of novel sulfated alpha-conotoxins from the cone snail Conus anemone. J Med Chem. 2004; 47(5):1234-41. DOI: 10.1021/jm031010o. View

Haberberger R, Bernardini N, Kress M, Hartmann P, Lips K, Kummer W . Nicotinic acetylcholine receptor subtypes in nociceptive dorsal root ganglion neurons of the adult rat. Auton Neurosci. 2004; 113(1-2):32-42. DOI: 10.1016/j.autneu.2004.05.008. View

Arredondo J, Nguyen V, Chernyavsky A, Bercovich D, Orr-Urtreger A, Kummer W . Central role of alpha7 nicotinic receptor in differentiation of the stratified squamous epithelium. J Cell Biol. 2002; 159(2):325-36. PMC: 2173052. DOI: 10.1083/jcb.200206096. View

Clark R, Fischer H, Nevin S, Adams D, Craik D . The synthesis, structural characterization, and receptor specificity of the alpha-conotoxin Vc1.1. J Biol Chem. 2006; 281(32):23254-63. DOI: 10.1074/jbc.M604550200. View

Vreugdenhil E, Jackson J, Bouwmeester T, Smit A, van Minnen J, Van Heerikhuizen H . Isolation, characterization, and evolutionary aspects of a cDNA clone encoding multiple neuropeptides involved in the stereotyped egg-laying behavior of the freshwater snail Lymnaea stagnalis. J Neurosci. 1988; 8(11):4184-91. PMC: 6569476. View

Kaplan N, Morpurgo N, Linial M . Novel families of toxin-like peptides in insects and mammals: a computational approach. J Mol Biol. 2007; 369(2):553-66. DOI: 10.1016/j.jmb.2007.02.106. View

Hone A, Whiteaker P, Christensen S, Xiao Y, Meyer E, McIntosh J . A novel fluorescent alpha-conotoxin for the study of alpha7 nicotinic acetylcholine receptors. J Neurochem. 2009; 111(1):80-9. PMC: 2749889. DOI: 10.1111/j.1471-4159.2009.06299.x. View

Luo S, Nguyen T, Cartier G, Olivera B, Yoshikami D, McIntosh J . Single-residue alteration in alpha-conotoxin PnIA switches its nAChR subtype selectivity. Biochemistry. 1999; 38(44):14542-8. DOI: 10.1021/bi991252j. View

10.

Sargent P . The diversity of neuronal nicotinic acetylcholine receptors. Annu Rev Neurosci. 1993; 16:403-43. DOI: 10.1146/annurev.ne.16.030193.002155. View

11.

Olivera B . Conus peptides: biodiversity-based discovery and exogenomics. J Biol Chem. 2006; 281(42):31173-7. DOI: 10.1074/jbc.R600020200. View

12.

Fry B, Roelants K, Champagne D, Scheib H, Tyndall J, King G . The toxicogenomic multiverse: convergent recruitment of proteins into animal venoms. Annu Rev Genomics Hum Genet. 2009; 10:483-511. DOI: 10.1146/annurev.genom.9.081307.164356. View

13.

Nevin S, Clark R, Klimis H, Christie M, Craik D, Adams D . Are alpha9alpha10 nicotinic acetylcholine receptors a pain target for alpha-conotoxins?. Mol Pharmacol. 2007; 72(6):1406-10. DOI: 10.1124/mol.107.040568. View

14.

Luo S, Zhangsun D, Zhang B, Quan Y, Wu Y . Novel alpha-conotoxins identified by gene sequencing from cone snails native to Hainan, and their sequence diversity. J Pept Sci. 2006; 12(11):693-704. DOI: 10.1002/psc.781. View

15.

Jakubowski J, Kelley W, Sweedler J, Gilly W, Schulz J . Intraspecific variation of venom injected by fish-hunting Conus snails. J Exp Biol. 2005; 208(Pt 15):2873-83. DOI: 10.1242/jeb.01713. View

16.

Fry B . From genome to "venome": molecular origin and evolution of the snake venom proteome inferred from phylogenetic analysis of toxin sequences and related body proteins. Genome Res. 2005; 15(3):403-20. PMC: 551567. DOI: 10.1101/gr.3228405. View

17.

Zhangsun D, Luo S, Wu Y, Zhu X, Hu Y, Xie L . Novel O-superfamily conotoxins identified by cDNA cloning from three vermivorous Conus species. Chem Biol Drug Des. 2006; 68(5):256-65. DOI: 10.1111/j.1747-0285.2006.00443.x. View

18.

Le Gall F, Favreau P, Richard G, Letourneux Y, Molgo J . The strategy used by some piscivorous cone snails to capture their prey: the effects of their venoms on vertebrates and on isolated neuromuscular preparations. Toxicon. 1999; 37(7):985-98. DOI: 10.1016/s0041-0101(98)00227-x. View

19.

Olivera B . E.E. Just Lecture, 1996. Conus venom peptides, receptor and ion channel targets, and drug design: 50 million years of neuropharmacology. Mol Biol Cell. 1997; 8(11):2101-9. PMC: 25694. DOI: 10.1091/mbc.8.11.2101. View

20.

Escoubas P, Corzo G, Whiteley B, Celerier M, Nakajima T . Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and high-performance liquid chromatography study of quantitative and qualitative variation in tarantula spider venoms. Rapid Commun Mass Spectrom. 2002; 16(5):403-13. DOI: 10.1002/rcm.595. View