skip to main content

Attention:

The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 11:00 PM ET on Friday, September 13 until 2:00 AM ET on Saturday, September 14 due to maintenance. We apologize for the inconvenience.

Explore Research Products in the NSF-PAR

Title: Venom production and secretion in reptiles
ABSTRACT The venom glands of reptiles, particularly those of front-fanged advanced snakes, must satisfy conflicting biological demands: rapid synthesis of potentially labile and highly toxic proteins, storage in the gland lumen for long periods, stabilization of the stored secretions, immediate activation of toxins upon deployment and protection of the animal from the toxic effects of its own venom. This dynamic system could serve as a model for the study of a variety of different phenomena involving exocrine gland activation, protein synthesis, stabilization of protein products and secretory mechanisms. However, these studies have been hampered by a lack of a long-term model that can be propagated in the lab (as opposed to whole-animal studies). Numerous attempts have been made to extend the lifetime of venom gland secretory cells, but only recently has an organoid model been shown to have the requisite qualities of recapitulation of the native system, self-propagation and long-term viability (>1 year). A tractable model is now available for myriad cell- and molecular-level studies of venom glands, protein synthesis and secretion. However, venom glands of reptiles are not identical, and many differ very extensively in overall architecture, microanatomy and protein products produced. This Review summarizes the similarities among and differences between venom glands of helodermatid lizards and of rear-fanged and front-fanged snakes, highlighting those areas that are well understood and identifying areas where future studies can fill in significant gaps in knowledge of these ancient, yet fascinating systems.  more » « less
Award ID(s):
1655571
NSF-PAR ID:
10321423
Author(s) / Creator(s):
Date Published:
Journal Name:
Journal of Experimental Biology
Volume:
225
Issue:
7
ISSN:
0022-0949
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. ; ; ; ; ( , Toxins)
    null (Ed.)
    The venoms of small rear-fanged snakes (RFS) remain largely unexplored, despite increased recognition of their importance in understanding venom evolution more broadly. Sequencing the transcriptome of venom-producing glands has greatly increased the ability of researchers to examine and characterize the toxin repertoire of small taxa with low venom yields. Here, we use RNA-seq to characterize the Duvernoy’s gland transcriptome of the Plains Black-headed Snake, Tantilla nigriceps, a small, semi-fossorial colubrid that feeds on a variety of potentially dangerous arthropods including centipedes and spiders. We generated transcriptomes of six individuals from three localities in order to both characterize the toxin expression of this species for the first time, and to look for initial evidence of venom variation in the species. Three toxin families—three-finger neurotoxins (3FTxs), cysteine-rich secretory proteins (CRISPs), and snake venom metalloproteinases (SVMPIIIs)—dominated the transcriptome of T. nigriceps; 3FTx themselves were the dominant toxin family in most individuals, accounting for as much as 86.4% of an individual’s toxin expression. Variation in toxin expression between individuals was also noted, with two specimens exhibiting higher relative expression of c-type lectins than any other sample (8.7–11.9% compared to <1%), and another expressed CRISPs higher than any other toxin. This study provides the first Duvernoy’s gland transcriptomes of any species of Tantilla, and one of the few transcriptomic studies of RFS not predicated on a single individual. This initial characterization demonstrates the need for further study of toxin expression variation in this species, as well as the need for further exploration of small RFS venoms. 
    more » « less
  2. ; ; ; ; ( , Scientific Reports)
    null (Ed.)
    Abstract Despite the extensive body of research on snake venom, many facets of snake venom systems, such as the physiology and regulation of the venom gland itself, remain virtually unstudied. Here, we use time series gene expression analyses of the rattlesnake venom gland in comparison with several non-venom tissues to characterize physiological and cellular processes associated with venom production and to highlight key distinctions of venom gland cellular and physiological function. We find consistent evidence for activation of stress response pathways in the venom gland, suggesting that mitigation of cellular stress is a crucial component of venom production. Additionally, we demonstrate evidence for an unappreciated degree of cellular and secretory activity in the steady state venom gland relative to other secretory tissues and identify vacuolar ATPases as the likely mechanisms driving acidification of the venom gland lumen during venom production and storage. 
    more » « less
  3. ; ; ; ; ; ; ( , Insect Systematics and Diversity)
    Bond, Jason (Ed.)
    Abstract

    Many herbivorous insect species are capable of hijacking plant development to induce novel plant organs called galls. In most groups of galling insects, the insect organs and molecular signals involved in gall induction are poorly understood. We focused on gall wasps (Hymenoptera:Cynipidae), the second largest clade of gall inducers (~1,400 spp.), for which the developmental stages and organs responsible for gall development are unclear. We investigated the female metasomal anatomy of 69 gall-inducing and 29 non-gall-inducing species across each of the major lineages of Cynipoidea, to test relationships between this lifestyle and the relative size of secretory organs. We confirmed that the venom apparatus in gall-inducing species is greatly expanded, although gall-inducing lineages vary in the relative size of these glands. Among these gallers, we measured the largest venom gland apparatus relative to body size ever recorded in insects. Non-galling inquiline species are accompanied by a reduction of this apparatus. Comparative microscopic analysis of venom glands suggests varying venom gland content across the lineages. Some oak gallers also had enlarged accessory glands, a lipid-rich organ whose function remains unclear, and which has not been previously studied in relation to gall formation. Together, the massive expansion of secretory organs specifically in gall-inducing species suggests a role of these secretions in the process of gall formation, and the variance in size of venom glands, accessory glands, and the contents of these glands among gallers, suggests that gall formation across this clade is likely to employ a diversity of molecular strategies.

     
    more » « less
  4. ; ; ; ; ; ; ; ( , BMC Biology)
    Abstract Background The explosive radiation and diversification of the advanced snakes (superfamily Colubroidea) was associated with changes in all aspects of the shared venom system. Morphological changes included the partitioning of the mixed ancestral glands into two discrete glands devoted for production of venom or mucous respectively, as well as changes in the location, size and structural elements of the venom-delivering teeth. Evidence also exists for homology among venom gland toxins expressed across the advanced snakes. However, despite the evolutionary novelty of snake venoms, in-depth toxin molecular evolutionary history reconstructions have been mostly limited to those types present in only two front-fanged snake families, Elapidae and Viperidae. To have a broader understanding of toxins shared among extant snakes, here we first sequenced the transcriptomes of eight taxonomically diverse rear-fanged species and four key viperid species and analysed major toxin types shared across the advanced snakes. Results Transcriptomes were constructed for the following families and species: Colubridae - Helicops leopardinus , Heterodon nasicus , Rhabdophis subminiatus ; Homalopsidae – Homalopsis buccata ; Lamprophiidae - Malpolon monspessulanus , Psammophis schokari , Psammophis subtaeniatus , Rhamphiophis oxyrhynchus ; and Viperidae – Bitis atropos , Pseudocerastes urarachnoides , Tropidolaeumus subannulatus , Vipera transcaucasiana . These sequences were combined with those from available databases of other species in order to facilitate a robust reconstruction of the molecular evolutionary history of the key toxin classes present in the venom of the last common ancestor of the advanced snakes, and thus present across the full diversity of colubroid snake venoms. In addition to differential rates of evolution in toxin classes between the snake lineages, these analyses revealed multiple instances of previously unknown instances of structural and functional convergences. Structural convergences included: the evolution of new cysteines to form heteromeric complexes, such as within kunitz peptides (the beta-bungarotoxin trait evolving on at least two occasions) and within SVMP enzymes (the P-IIId trait evolving on at least three occasions); and the C-terminal tail evolving on two separate occasions within the C-type natriuretic peptides, to create structural and functional analogues of the ANP/BNP tailed condition. Also shown was that the de novo evolution of new post-translationally liberated toxin families within the natriuretic peptide gene propeptide region occurred on at least five occasions, with novel functions ranging from induction of hypotension to post-synaptic neurotoxicity. Functional convergences included the following: multiple occasions of SVMP neofunctionalised in procoagulant venoms into activators of the clotting factors prothrombin and Factor X; multiple instances in procoagulant venoms where kunitz peptides were neofunctionalised into inhibitors of the clot destroying enzyme plasmin, thereby prolonging the half-life of the clots formed by the clotting activating enzymatic toxins; and multiple occasions of kunitz peptides neofunctionalised into neurotoxins acting on presynaptic targets, including twice just within Bungarus venoms. Conclusions We found novel convergences in both structural and functional evolution of snake toxins. These results provide a detailed roadmap for future work to elucidate predator–prey evolutionary arms races, ascertain differential clinical pathologies, as well as documenting rich biodiscovery resources for lead compounds in the drug design and discovery pipeline. 
    more » « less
  5. ; ; ; ; ; ; ; ; ; ; et al ( , Toxins)
    null (Ed.)
    Ontogenetic changes in venom composition have been described in Bothrops snakes, but only a few studies have attempted to identify the targeted paralogues or the molecular mechanisms involved in modifications of gene expression during ontogeny. In this study, we decoded B. jararacussu venom gland transcripts from six specimens of varying sizes and analyzed the variability in the composition of independent venom proteomes from 19 individuals. We identified 125 distinct putative toxin transcripts, and of these, 73 were detected in venom proteomes and only 10 were involved in the ontogenetic changes. Ontogenetic variability was linearly related to snake size and did not correspond to the maturation of the reproductive stage. Changes in the transcriptome were highly predictive of changes in the venom proteome. The basic myotoxic phospholipases A2 (PLA2s) were the most abundant components in larger snakes, while in venoms from smaller snakes, PIII-class SVMPs were the major components. The snake venom metalloproteinases (SVMPs) identified corresponded to novel sequences and conferred higher pro-coagulant and hemorrhagic functions to the venom of small snakes. The mechanisms modulating venom variability are predominantly related to transcriptional events and may consist of an advantage of higher hematotoxicity and more efficient predatory function in the venom from small snakes. 
    more » « less
  • Citation Formats
  • MLA
  • APA
  • Chicago
  • BibTeX
  • Save / Share this Record
  • Send to Email