title: Hormone-like peptides in the venoms of marine cone snails.
abstract: The venoms of cone snails (genus Conus) are remarkably complex, consisting of hundreds of typically short, disulfide-rich peptides termed conotoxins. These peptides have diverse pharmacological targets, with injection of venom eliciting a range of physiological responses, including sedation, paralysis and sensory overload. Most conotoxins target the prey's nervous system but evidence of venom peptides targeting neuroendocrine processes is emerging. Examples include vasopressin, RFamide neuropeptides and recently also insulin. To investigate the diversity of hormone/neuropeptide-like molecules in the venoms of cone snails we systematically mined the venom gland transcriptomes of several cone snail species and examined secreted venom peptides in dissected and injected venom of the Australian cone snail Conus victoriae. Using this approach we identified several novel hormone/neuropeptide-like toxins, including peptides similar to the bee brain hormone prohormone-4, the mollusc ganglia neuropeptide elevenin, and thyrostimulin, a member of the glycoprotein hormone family, and confirmed the presence of insulin. We confirmed that at least two of these peptides are not only expressed in the venom gland but also form part of the injected venom cocktail, unambiguously demonstrating their role in envenomation. Our findings suggest that hormone/neuropeptide-like toxins are a diverse and integral part of the complex envenomation strategy of Conus. Exploration of this group of venom components offers an exciting new avenue for the discovery of novel pharmacological tools and drug candidates, complementary to conotoxins.
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia. Electronic address: sam.robinson@utah.edu.
authors: Samuel D
authors: SD
authors: Robinson
authors: Eccles Institute of Human Genetics, University of Utah, and School of Medicine, Salt Lake City, UT 84112, USA.
authors: Qing
authors: Q
authors: Li
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
authors: Pradip K
authors: PK
authors: Bandyopadhyay
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA.
authors: Joanna
authors: J
authors: Gajewiak
authors: Eccles Institute of Human Genetics, University of Utah, and School of Medicine, Salt Lake City, UT 84112, USA.
authors: Mark
authors: M
authors: Yandell
authors: Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
authors: Anthony T
authors: AT
authors: Papenfuss
authors: The Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
authors: Anthony W
authors: AW
authors: Purcell
authors: Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors: Raymond S
authors: RS
authors: Norton
authors: Department of Biology, University of Utah, Salt Lake City, UT 84112, USA; Department of Biology, Copenhagen Biocenter, Ole Maaløes Vej 5, DK-2200 Copenhagen, Denmark. Electronic address: safavihelena@gmail.com.
authors: Helena
authors: H
authors: Safavi-Hemami
mesh_terms: D000818:Animals; D020916:Conotoxins; D010455:Peptides / Q000378:metabolism*; D012908:Snails; D014688:Venoms / Q000378:metabolism*
chemical_list: D020916:Conotoxins; D010455:Peptides; D014688:Venoms
keywords: Conotoxin; Elevenin; Hormone; Neuropeptide; Prohormone-4; Venom