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Fish-hunting cone snail disrupts prey’s glucose homeostasis with weaponized mimetics of somatostatin and insulin

Yeung, Ho Yan ; Ramiro, Iris Bea L. ; Andersen, Daniel B. ; Koch, Thomas Lund ; Hamilton, Alexander LU ; Bjørn-Yoshimoto, Walden E. ; Espino, Samuel ; Vakhrushev, Sergey Y. ; Pedersen, Kasper B. and de Haan, Noortje , et al. (2024) In Nature Communications 15(1).
Abstract

Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective somatostatin receptor 2 (SSTR2) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with... (More)

Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective somatostatin receptor 2 (SSTR2) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin’s N-terminal tail closely mimics a glycosylated somatostatin from fish pancreas and is crucial for activating the fish SSTR2. Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture.

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type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
15
issue
1
article number
6408
publisher
Nature Publishing Group
external identifiers
  • scopus:85201634214
  • pmid:39164229
ISSN
2041-1723
DOI
10.1038/s41467-024-50470-2
language
English
LU publication?
yes
id
b0e5ffa0-71bd-407a-a06a-b5aaceaf1e90
date added to LUP
2024-10-28 14:03:03
date last changed
2024-11-11 16:38:10
@article{b0e5ffa0-71bd-407a-a06a-b5aaceaf1e90,
  abstract     = {{<p>Venomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective somatostatin receptor 2 (SSTR<sub>2</sub>) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin’s N-terminal tail closely mimics a glycosylated somatostatin from fish pancreas and is crucial for activating the fish SSTR<sub>2</sub>. Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture.</p>}},
  author       = {{Yeung, Ho Yan and Ramiro, Iris Bea L. and Andersen, Daniel B. and Koch, Thomas Lund and Hamilton, Alexander and Bjørn-Yoshimoto, Walden E. and Espino, Samuel and Vakhrushev, Sergey Y. and Pedersen, Kasper B. and de Haan, Noortje and Hipgrave Ederveen, Agnes L. and Olivera, Baldomero M. and Knudsen, Jakob G. and Bräuner-Osborne, Hans and Schjoldager, Katrine T. and Holst, Jens Juul and Safavi-Hemami, Helena}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Fish-hunting cone snail disrupts prey’s glucose homeostasis with weaponized mimetics of somatostatin and insulin}},
  url          = {{http://dx.doi.org/10.1038/s41467-024-50470-2}},
  doi          = {{10.1038/s41467-024-50470-2}},
  volume       = {{15}},
  year         = {{2024}},
}