scholarly journals Insights into the origins of fish hunting in venomous cone snails from studies of Conus tessulatus

2015 ◽  
Vol 112 (16) ◽  
pp. 5087-5092 ◽  
Author(s):  
Joseph W. Aman ◽  
Julita S. Imperial ◽  
Beatrix Ueberheide ◽  
Min-Min Zhang ◽  
Manuel Aguilar ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Molecular Mechanisms ◽  
Prey Capture ◽  
Sequence Similarity ◽  
Cone Snail ◽  
Evolutionary Transitions ◽  
Voltage Gated ◽  
Channel Inactivation ◽  
Voltage Gated Sodium Channels ◽  
Cone Snails

Prey shifts in carnivorous predators are events that can initiate the accelerated generation of new biodiversity. However, it is seldom possible to reconstruct how the change in prey preference occurred. Here we describe an evolutionary “smoking gun” that illuminates the transition from worm hunting to fish hunting among marine cone snails, resulting in the adaptive radiation of fish-hunting lineages comprising ∼100 piscivorous Conus species. This smoking gun is δ-conotoxin TsVIA, a peptide from the venom of Conus tessulatus that delays inactivation of vertebrate voltage-gated sodium channels. C. tessulatus is a species in a worm-hunting clade, which is phylogenetically closely related to the fish-hunting cone snail specialists. The discovery of a δ-conotoxin that potently acts on vertebrate sodium channels in the venom of a worm-hunting cone snail suggests that a closely related ancestral toxin enabled the transition from worm hunting to fish hunting, as δ-conotoxins are highly conserved among fish hunters and critical to their mechanism of prey capture; this peptide, δ-conotoxin TsVIA, has striking sequence similarity to these δ-conotoxins from piscivorous cone snail venoms. Calcium-imaging studies on dissociated dorsal root ganglion (DRG) neurons revealed the peptide’s putative molecular target (voltage-gated sodium channels) and mechanism of action (inhibition of channel inactivation). The results were confirmed by electrophysiology. This work demonstrates how elucidating the specific interactions between toxins and receptors from phylogenetically well-defined lineages can uncover molecular mechanisms that underlie significant evolutionary transitions.

scholarly journals Distribution of TTX-sensitive voltage-gated sodium channels in primary sensory endings of mammalian muscle spindles

2017 ◽  
Vol 117 (4) ◽  
pp. 1690-1701 ◽  
Author(s):  
Dario I. Carrasco ◽  
Jacob A. Vincent ◽  
Timothy C. Cope
Keyword(s):  
Sodium Channels ◽  
Molecular Mechanisms ◽  
Mammalian Species ◽  
Muscle Spindles ◽  
Tonic Firing ◽  
Muscle Stretch ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Nav Channels ◽  
Sensory Endings

Knowledge of the molecular mechanisms underlying signaling of mechanical stimuli by muscle spindles remains incomplete. In particular, the ionic conductances that sustain tonic firing during static muscle stretch are unknown. We hypothesized that tonic firing by spindle afferents depends on sodium persistent inward current (INaP) and tested for the necessary presence of the appropriate voltage-gated sodium (NaV) channels in primary sensory endings. The NaV1.6 isoform was selected for both its capacity to produce INaP and for its presence in other mechanosensors that fire tonically. The present study shows that NaV1.6 immunoreactivity (IR) is concentrated in heminodes, presumably where tonic firing is generated, and we were surprised to find NaV1.6 IR strongly expressed also in the sensory terminals, where mechanotransduction occurs. This spatial pattern of NaV1.6 IR distribution was consistent for three mammalian species (rat, cat, and mouse), as was tonic firing by primary spindle afferents. These findings meet some of the conditions needed to establish participation of INaP in tonic firing by primary sensory endings. The study was extended to two additional NaV isoforms, selected for their sensitivity to TTX, excluding TTX-resistant NaV channels, which alone are insufficient to support firing by primary spindle endings. Positive immunoreactivity was found for NaV1.1, predominantly in sensory terminals together with NaV1.6 and for NaV1.7, mainly in preterminal axons. Differential distribution in primary sensory endings suggests specialized roles for these three NaV isoforms in the process of mechanosensory signaling by muscle spindles. NEW & NOTEWORTHY The molecular mechanisms underlying mechanosensory signaling responsible for proprioceptive functions are not completely elucidated. This study provides the first evidence that voltage-gated sodium channels (NaVs) are expressed in the spindle primary sensory ending, where NaVs are found at every site involved in transduction or encoding of muscle stretch. We propose that NaVs contribute to multiple steps in sensory signaling by muscle spindles as it does in other types of slowly adapting sensory neurons.

scholarly journals Voltage-Gated Sodium Channels: A Prominent Target of Marine Toxins

Marine Drugs ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. 562
Author(s):  
Rawan Mackieh ◽  
Rita Abou-Nader ◽  
Rim Wehbe ◽  
César Mattei ◽  
Christian Legros ◽  
...  
Keyword(s):  
Sodium Channels ◽  
Physiological Role ◽  
Supporting Cell ◽  
Cone Snail ◽  
Marine Toxins ◽  
Marine Animals ◽  
Communication Signals ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Wide Range

Voltage-gated sodium channels (VGSCs) are considered to be one of the most important ion channels given their remarkable physiological role. VGSCs constitute a family of large transmembrane proteins that allow transmission, generation, and propagation of action potentials. This occurs by conducting Na+ ions through the membrane, supporting cell excitability and communication signals in various systems. As a result, a wide range of coordination and physiological functions, from locomotion to cognition, can be accomplished. Drugs that target and alter the molecular mechanism of VGSCs’ function have highly contributed to the discovery and perception of the function and the structure of this channel. Among those drugs are various marine toxins produced by harmful microorganisms or venomous animals. These toxins have played a key role in understanding the mode of action of VGSCs and in mapping their various allosteric binding sites. Furthermore, marine toxins appear to be an emerging source of therapeutic tools that can relieve pain or treat VGSC-related human channelopathies. Several studies documented the effect of marine toxins on VGSCs as well as their pharmaceutical applications, but none of them underlined the principal marine toxins and their effect on VGSCs. Therefore, this review aims to highlight the neurotoxins produced by marine animals such as pufferfish, shellfish, sea anemone, and cone snail that are active on VGSCs and discuss their pharmaceutical values.

scholarly journals Neurotoxic peptides from the venom of the giant Australian stinging tree

2020 ◽  
Vol 6 (38) ◽  
pp. eabb8828
Author(s):  
Edward K. Gilding ◽  
Sina Jami ◽  
Jennifer R. Deuis ◽  
Mathilde R. Israel ◽  
Peta J. Harvey ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Sodium Channels ◽  
Sensory Neurons ◽  
Convergent Evolution ◽  
3D Structure ◽  
Cone Snail ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Sensory Effects ◽  
Mammalian Skin

Stinging trees from Australasia produce remarkably persistent and painful stings upon contact of their stiff epidermal hairs, called trichomes, with mammalian skin. Dendrocnide-induced acute pain typically lasts for several hours, and intermittent painful flares can persist for days and weeks. Pharmacological activity has been attributed to small-molecule neurotransmitters and inflammatory mediators, but these compounds alone cannot explain the observed sensory effects. We show here that the venoms of Australian Dendrocnide species contain heretofore unknown pain-inducing peptides that potently activate mouse sensory neurons and delay inactivation of voltage-gated sodium channels. These neurotoxins localize specifically to the stinging hairs and are miniproteins of 4 kDa, whose 3D structure is stabilized in an inhibitory cystine knot motif, a characteristic shared with neurotoxins found in spider and cone snail venoms. Our results provide an intriguing example of inter-kingdom convergent evolution of animal and plant venoms with shared modes of delivery, molecular structure, and pharmacology.

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