scholarly journals Electric Blue: Molecular Evolution of Three-Finger Toxins in the Long-Glanded Coral Snake Species Calliophis bivirgatus

Toxins ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 124
Author(s):  
Daniel Dashevsky ◽  
Darin Rokyta ◽  
Nathaniel Frank ◽  
Amanda Nouwens ◽  
Bryan G. Fry

The genus Calliophis is the most basal branch of the family Elapidae and several species in it have developed highly elongated venom glands. Recent research has shown that C. bivirgatus has evolved a seemingly unique toxin (calliotoxin) that produces spastic paralysis in their prey by acting on the voltage-gated sodium (NaV) channels. We assembled a transcriptome from C. bivirgatus to investigate the molecular characteristics of these toxins and the venom as a whole. We find strong confirmation that this genus produces the classic elapid eight-cysteine three-finger toxins, that δδ-elapitoxins (toxins that resemble calliotoxin) are responsible for a substantial portion of the venom composition, and that these toxins form a distinct clade within a larger, more diverse clade of C. bivirgatus three-finger toxins. This broader clade of C. bivirgatus toxins also contains the previously named maticotoxins and is somewhat closely related to cytotoxins from other elapids. However, the toxins from this clade that have been characterized are not themselves cytotoxic. No other toxins show clear relationships to toxins of known function from other species.

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Jianke Du ◽  
Chunfeng Ge ◽  
Tingting Li ◽  
Sanhong Wang ◽  
Zhihong Gao ◽  
...  

AbstractStrawberry (Fragaria spp.) is a member of the Rosoideae subfamily in the family Rosaceae. The self-incompatibility (SI) of some diploid species is a key agronomic trait that acts as a basic pollination barrier; however, the genetic mechanism underlying SI control in strawberry remains unclear. Two candidate S-RNases (Sa- and Sb-RNase) identified in the transcriptome of the styles of the self-incompatible Fragaria viridis 42 were confirmed to be SI determinants at the S locus following genotype identification and intraspecific hybridization using selfing progenies. Whole-genome collinearity and RNase T2 family analysis revealed that only an S locus exists in Fragaria; however, none of the compatible species contained S-RNase. Although the results of interspecific hybridization experiments showed that F. viridis (SI) styles could accept pollen from F. mandshurica (self-compatible), the reciprocal cross was incompatible. Sa and Sb-RNase contain large introns, and their noncoding sequences (promotors and introns) can be transcribed into long noncoding RNAs (lncRNAs). Overall, the genus Fragaria exhibits S-RNase-based gametophytic SI, and S-RNase loss occurs at the S locus of compatible germplasms. In addition, a type of SI-independent unilateral incompatibility exists between compatible and incompatible Fragaria species. Furthermore, the large introns and neighboring lncRNAs in S-RNase in Fragaria could offer clues about S-RNase expression strategies.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Luo ◽  
Yiying Ding ◽  
Zhihao Peng ◽  
Kezhi Chen ◽  
Xuewen Zhang ◽  
...  

AbstractHeteropoda venatoria in the family Sparassidae is highly valued in pantropical countries because the species feed on domestic insect pests. Unlike most other species of Araneomorphae, H. venatoria uses the great speed and strong chelicerae (mouthparts) with toxin glands to capture the insects instead of its web. Therefore, H. venatoria provides unique opportunities for venom evolution research. The venom of H. venatoria was explored by matrix-assisted laser desorption/ionization tandem time-of-flight and analyzing expressed sequence tags. The 154 sequences coding cysteine-rich peptides (CRPs) revealed 24 families based on the phylogenetic analyses of precursors and cysteine frameworks in the putative mature regions. Intriguingly, four kinds of motifs are first described in spider venom. Furthermore, combining the diverse CRPs of H. venatoria with previous spider venom peptidomics data, the structures of precursors and the patterns of cysteine frameworks were analyzed. This work revealed the dynamic evolutionary trends of venom CRPs in H. venatoria: the precursor has evolved an extended mature peptide with more cysteines, and a diminished or even vanished propeptides between the signal and mature peptides; and the CRPs evolved by multiple duplications of an ancestral ICK gene as well as recruitments of non-toxin genes.


1997 ◽  
Vol 75 (7) ◽  
pp. 1014-1019 ◽  
Author(s):  
E. Schoeters ◽  
J. Billen ◽  
J. O. Schmidt

Spider wasps, i.e., the family Pompilidae, in general, and those belonging to the genus Pepsis in particular, are acknowledged to possess venoms that are algogenic to humans and thus have the parsimonious functions of causing paralysis and providing defense against predators. The morphological organization of the venom system and its complex convoluted gland closely resembles that in social members of the Vespidae. These features distinguish the venom glands of the Pompilidae from those of the sibling family Mutillidae as well as those of the family Sphecidae, which lack convoluted glands. Although the venom glands in Pepsis species are very similar in morphology to those of social vespids, the lethality of Pepsis venom to mammals is several times less than that of the social common wasps. These findings suggest that in terms of the evolution of venom activity and the associated glandular structures, there was apparently no need for social wasps to develop extra parts of the venom system for producing toxic, lethal, or powerful algogenic components. All of the glandular parts of the venom gland of social wasps were already present in pompilids (and eumenids) and, presumably, in their ancestors.


eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Naomi AK Hanemaaijer ◽  
Marko A Popovic ◽  
Xante Wilders ◽  
Sara Grasman ◽  
Oriol Pavón Arocas ◽  
...  

Calcium ions (Ca2+) are essential for many cellular signaling mechanisms and enter the cytosol mostly through voltage-gated calcium channels. Here, using high-speed Ca2+ imaging up to 20 kHz in the rat layer five pyramidal neuron axon we found that activity-dependent intracellular calcium concentration ([Ca2+]i) in the axonal initial segment was only partially dependent on voltage-gated calcium channels. Instead, [Ca2+]i changes were sensitive to the specific voltage-gated sodium (NaV) channel blocker tetrodotoxin. Consistent with the conjecture that Ca2+ enters through the NaV channel pore, the optically resolved ICa in the axon initial segment overlapped with the activation kinetics of NaV channels and heterologous expression of NaV1.2 in HEK-293 cells revealed a tetrodotoxin-sensitive [Ca2+]i rise. Finally, computational simulations predicted that axonal [Ca2+]i transients reflect a 0.4% Ca2+ conductivity of NaV channels. The findings indicate that Ca2+ permeation through NaV channels provides a submillisecond rapid entry route in NaV-enriched domains of mammalian axons.


Toxins ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 626 ◽  
Author(s):  
Yashad Dongol ◽  
Fernanda Caldas Cardoso ◽  
Richard J Lewis

Voltage-gated sodium channels (NaVs) are a key determinant of neuronal signalling. Neurotoxins from diverse taxa that selectively activate or inhibit NaV channels have helped unravel the role of NaV channels in diseases, including chronic pain. Spider venoms contain the most diverse array of inhibitor cystine knot (ICK) toxins (knottins). This review provides an overview on how spider knottins modulate NaV channels and describes the structural features and molecular determinants that influence their affinity and subtype selectivity. Genetic and functional evidence support a major involvement of NaV subtypes in various chronic pain conditions. The exquisite inhibitory properties of spider knottins over key NaV subtypes make them the best lead molecules for the development of novel analgesics to treat chronic pain.


Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 501
Author(s):  
Dominique Koua ◽  
Rosanna Mary ◽  
Anicet Ebou ◽  
Celia Barrachina ◽  
Khadija El Koulali ◽  
...  

Spider venoms represent an original source of novel compounds with therapeutic and agrochemical potential. Whereas most of the research efforts have focused on large mygalomorph spiders, araneomorph spiders are equally promising but require more sensitive and sophisticated approaches given their limited size and reduced venom yield. Belonging to the latter group, the genus Lycosa (“wolf spiders”) contains many species widely distributed throughout the world. These spiders are ambush predators that do not build webs but instead rely strongly on their venom for prey capture. Lycosa tarantula is one of the largest species of wolf spider, but its venom composition is unknown. Using a combination of RNA sequencing of the venom glands and venom proteomics, we provide the first overview of the peptides and proteins produced by this iconic Mediterranean spider. Beside the typical small disulfide rich neurotoxins, several families of proteins were also identified, including cysteine-rich secretory proteins (CRISP) and Hyaluronidases. Proteomic analysis of the electrically stimulated venom validated 30 of these transcriptomic sequences, including nine putative neurotoxins and eight venom proteins. Interestingly, LC-MS venom profiles of manual versus electric stimulation, as well as female versus male, showed some marked differences in mass distribution. Finally, we also present some preliminary data on the biological activity of L. tarantula crude venom.


Author(s):  
J.R. Patel ◽  
S. Didlick

There are at least 16 recognised herpesviruses that naturally infect cattle, sheep, goats and various species of deer and antelopes. Six of the viruses are recognised as distinct alphaherpesviruses and 9 as gammaherpesviruses. Buffalo herpesvirus (BflHV) and ovine herpesvirus-1 (OvHV-1) remain officially unclassified. The prevalence of ruminant herpesviruses varies from worldwide to geographically restricted in distribution. Viruses in both subfamilies Alphaherpesvirinae and Gammaherpesvirinae cause mild to moderate and severe disease in respective natural or secondary ruminant hosts. Accordingly, the economic and ecological impact of the viruses is also variable. The molecular characteristics of some members have been investigated in detail. This has led to the identification of virulence-associated genes and construction of deletion mutants and recombinant viruses. Some of the latter have been developed as commercial vaccines. This paper aims to give an overview of the epidemiology and pathogenesis of infection by these viruses, immuno-prophylaxis and mechanisms of recovery from infection. Since there are 128 ruminant species in the family Bovidae, it is likely that some herpesviruses remain undiscovered. We conclude that currently known ruminant alphaherpesviruses occur only in their natural hosts and do not cross stably into other ruminant species. By contrast, gammaherpesviruses have a much broader host range as evidenced by the fact that antibodies reactive to alcelaphine herpesvirus type 1 have been detected in 4 subfamilies in the family Bovidae, namely Alcelaphinae, Hippotraginae, Ovibovinae and Caprinae. New gammaherpesviruses within these subfamilies are likely to be discovered in the future.


Pain ◽  
2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Joel Castro ◽  
Jessica Maddern ◽  
Andelain Erickson ◽  
Ashlee Caldwell ◽  
Luke Grundy ◽  
...  

2015 ◽  
Vol 147 (1) ◽  
pp. 1-24 ◽  
Author(s):  
Christopher A. Ahern ◽  
Jian Payandeh ◽  
Frank Bosmans ◽  
Baron Chanda

Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts.


eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Paul G DeCaen ◽  
Yuka Takahashi ◽  
Terry A Krulwich ◽  
Masahiro Ito ◽  
David E Clapham

Entry and extrusion of cations are essential processes in living cells. In alkaliphilic prokaryotes, high external pH activates voltage-gated sodium channels (Nav), which allows Na+ to enter and be used as substrate for cation/proton antiporters responsible for cytoplasmic pH homeostasis. Here, we describe a new member of the prokaryotic voltage-gated Na+ channel family (NsvBa; Non-selective voltage-gated, Bacillus alcalophilus) that is nonselective among Na+, Ca2+ and K+ ions. Mutations in NsvBa can convert the nonselective filter into one that discriminates for Na+ or divalent cations. Gain-of-function experiments demonstrate the portability of ion selectivity with filter mutations to other Bacillus Nav channels. Increasing pH and temperature shifts their activation threshold towards their native resting membrane potential. Furthermore, we find drugs that target Bacillus Nav channels also block the growth of the bacteria. This work identifies some of the adaptations to achieve ion discrimination and gating in Bacillus Nav channels.


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