Specialized insulin is used for chemical warfare by fish-hunting cone snails

Helena Safavi-Hemami, Joanna Gajewiak, Santhosh Karanth, Samuel Robinson, Beatrix Ueberheide, Adam D Douglass, Amnon Schlegel, Julita S Imperial, Maren Watkins, Pradip K Bandyopadhyay, Mark Yandell, Qing Li, Anthony Wayne Purcell, Raymond Stanley Norton, Lars Ellgaard, Baldomero Marquez Olivera

Research output: Contribution to journalArticleResearchpeer-review

Abstract

More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that post-translational modifications characteristic of conotoxins (hydroxyproline, ?-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snails distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.
Original languageEnglish
Pages (from-to)1743 - 1748
Number of pages6
JournalProceedings of the National Academy of Sciences
Volume112
Issue number6
DOIs
Publication statusPublished - 2015

Cite this

Safavi-Hemami, H., Gajewiak, J., Karanth, S., Robinson, S., Ueberheide, B., Douglass, A. D., ... Olivera, B. M. (2015). Specialized insulin is used for chemical warfare by fish-hunting cone snails. Proceedings of the National Academy of Sciences, 112(6), 1743 - 1748. https://doi.org/10.1073/pnas.1423857112
Safavi-Hemami, Helena ; Gajewiak, Joanna ; Karanth, Santhosh ; Robinson, Samuel ; Ueberheide, Beatrix ; Douglass, Adam D ; Schlegel, Amnon ; Imperial, Julita S ; Watkins, Maren ; Bandyopadhyay, Pradip K ; Yandell, Mark ; Li, Qing ; Purcell, Anthony Wayne ; Norton, Raymond Stanley ; Ellgaard, Lars ; Olivera, Baldomero Marquez. / Specialized insulin is used for chemical warfare by fish-hunting cone snails. In: Proceedings of the National Academy of Sciences. 2015 ; Vol. 112, No. 6. pp. 1743 - 1748.
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abstract = "More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that post-translational modifications characteristic of conotoxins (hydroxyproline, ?-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snails distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.",
author = "Helena Safavi-Hemami and Joanna Gajewiak and Santhosh Karanth and Samuel Robinson and Beatrix Ueberheide and Douglass, {Adam D} and Amnon Schlegel and Imperial, {Julita S} and Maren Watkins and Bandyopadhyay, {Pradip K} and Mark Yandell and Qing Li and Purcell, {Anthony Wayne} and Norton, {Raymond Stanley} and Lars Ellgaard and Olivera, {Baldomero Marquez}",
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language = "English",
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Safavi-Hemami, H, Gajewiak, J, Karanth, S, Robinson, S, Ueberheide, B, Douglass, AD, Schlegel, A, Imperial, JS, Watkins, M, Bandyopadhyay, PK, Yandell, M, Li, Q, Purcell, AW, Norton, RS, Ellgaard, L & Olivera, BM 2015, 'Specialized insulin is used for chemical warfare by fish-hunting cone snails' Proceedings of the National Academy of Sciences, vol. 112, no. 6, pp. 1743 - 1748. https://doi.org/10.1073/pnas.1423857112

Specialized insulin is used for chemical warfare by fish-hunting cone snails. / Safavi-Hemami, Helena; Gajewiak, Joanna; Karanth, Santhosh; Robinson, Samuel; Ueberheide, Beatrix; Douglass, Adam D; Schlegel, Amnon; Imperial, Julita S; Watkins, Maren; Bandyopadhyay, Pradip K; Yandell, Mark; Li, Qing; Purcell, Anthony Wayne; Norton, Raymond Stanley; Ellgaard, Lars; Olivera, Baldomero Marquez.

In: Proceedings of the National Academy of Sciences, Vol. 112, No. 6, 2015, p. 1743 - 1748.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Specialized insulin is used for chemical warfare by fish-hunting cone snails

AU - Safavi-Hemami, Helena

AU - Gajewiak, Joanna

AU - Karanth, Santhosh

AU - Robinson, Samuel

AU - Ueberheide, Beatrix

AU - Douglass, Adam D

AU - Schlegel, Amnon

AU - Imperial, Julita S

AU - Watkins, Maren

AU - Bandyopadhyay, Pradip K

AU - Yandell, Mark

AU - Li, Qing

AU - Purcell, Anthony Wayne

AU - Norton, Raymond Stanley

AU - Ellgaard, Lars

AU - Olivera, Baldomero Marquez

PY - 2015

Y1 - 2015

N2 - More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that post-translational modifications characteristic of conotoxins (hydroxyproline, ?-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snails distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.

AB - More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that post-translational modifications characteristic of conotoxins (hydroxyproline, ?-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snails distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.

UR - http://www.pnas.org/content/112/6/1743.full.pdf

U2 - 10.1073/pnas.1423857112

DO - 10.1073/pnas.1423857112

M3 - Article

VL - 112

SP - 1743

EP - 1748

JO - Proceedings of the National Academy of Sciences

JF - Proceedings of the National Academy of Sciences

SN - 0027-8424

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Safavi-Hemami H, Gajewiak J, Karanth S, Robinson S, Ueberheide B, Douglass AD et al. Specialized insulin is used for chemical warfare by fish-hunting cone snails. Proceedings of the National Academy of Sciences. 2015;112(6):1743 - 1748. https://doi.org/10.1073/pnas.1423857112