Molecular cloning, heterologous expression and functional characterization of a novel translationally-controlled tumor protein (TCTP) family member from Loxosceles intermedia (brown spider) venom

Sade, Youssef Bacila; Bóia-Ferreira, Marianna; Gremski, Luiza Helena; Silveira, Rafael Bertoni da; Gremski, Waldemiro; Senff‐Ribeiro, Andrea; Chaim, Olga Meiri; Veiga, Sílvio Sanches

doi:10.1016/j.biocel.2011.10.013

Cited by 44 publications

(57 citation statements)

References 56 publications

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“…A transcript resembling the TCTP was consistently expressed at high levels across all tissue types in our focal species (table 3) and also expressed at high levels previously in acrorhagi of A. elegantissima (see Macrander, Brugler, et al 2015). Venomous TCTP toxins induce vascular permeability, resulting in an inflammatory response (Rattmann et al 2008; Sade et al 2012) which is likely due to their ability to target mast cells, releasing histamine that can ultimately cause pain, edema, and erythema (Mulenga and Azad 2005; Sade et al 2012). Symptoms exhibited by TCTP toxins in noncnidarian lineages resemble that of thalassine, an uncharacterized component in sea anemone venom described early on in sea anemone venom research (Richet 1903a, 1903b, 1905).…”

Section: Discussionmentioning

confidence: 99%

Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones

2016

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Cnidarians represent one of the few groups of venomous animals that lack a centralized venom transmission system. Instead, they are equipped with stinging capsules collectively known as nematocysts. Nematocysts vary in abundance and type across different tissues; however, the venom composition in most species remains unknown. Depending on the tissue type, the venom composition in sea anemones may be vital for predation, defense, or digestion. Using a tissue-specific RNA-seq approach, we characterize the venom assemblage in the tentacles, mesenterial filaments, and column for three species of sea anemone (Anemonia sulcata, Heteractis crispa, and Megalactis griffithsi). These taxa vary with regard to inferred venom potency, symbiont abundance, and nematocyst diversity. We show that there is significant variation in abundance of toxin-like genes across tissues and species. Although the cumulative toxin abundance for the column was consistently the lowest, contributions to the overall toxin assemblage varied considerably among tissues for different toxin types. Our gene ontology (GO) analyses also show sharp contrasts between conserved GO groups emerging from whole transcriptome analysis and tissue-specific expression among GO groups in our differential expression analysis. This study provides a framework for future characterization of tissue-specific venom and other functionally important genes in this lineage of simple bodied animals.

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Section: Discussionmentioning

confidence: 99%

Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones

2016

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“…the participation in the deadly cocktail of spider venoms. Two papers reported that translationally controlled tumour protein is a component of the venom from the brown spider Loxosceles intermedia (Gremski et al 2014;Sade et al 2012). Another one investigated the spit (used to 'glue' the prey to a solid surface) and the venom of the spider Scytodes thoracica using transcriptomic and proteomic analyses.…”

Section: Tctp In Arthropodsmentioning

confidence: 99%

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

Bommer

2017

Results and Problems in Cell Differentiation

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The Translational Controlled Tumour Protein TCTP (gene symbol TPT1, also called P21, P23, Q23, fortilin or histamine-releasing factor, HRF) is a highly conserved protein present in essentially all eukaryotic organisms and involved in many fundamental cell biological and disease processes. It was first discovered about 35 years ago, and it took an extended period of time for its multiple functions to be revealed, and even today we do not yet fully understand all the details. Having witnessed most of this history, in this chapter, I give a brief overview and review the current knowledge on the structure, biological functions, disease involvements and cellular regulation of this protein. TCTP is able to interact with a large number of other proteins and is therefore involved in many core cell biological processes, predominantly in the response to cellular stresses, such as oxidative stress, heat shock, genotoxic stress, imbalance of ion metabolism as well as other conditions. Mechanistically, TCTP acts as an anti-apoptotic protein, and it is involved in DNA-damage repair and in cellular autophagy. Thus, broadly speaking, TCTP can be considered a cytoprotective protein. In addition, TCTP facilitates cell division through stabilising the mitotic spindle and cell growth through modulating growth signalling pathways and through its interaction with the proteosynthetic machinery of the cell. Due to its activities, both as an anti-apoptotic protein and in promoting cell growth and division, TCTP is also essential in the early development of both animals and plants. Apart from its involvement in various biological processes at the cellular level, TCTP can also act as an extracellular protein and as such has been involved in modulating whole-body defence processes, namely in the mammalian immune system. Extracellular TCTP, typically in its dimerised form, is able to induce the release of cytokines and other signalling molecules from various types of immune cells. There are also several examples, where TCTP was shown to be involved in antiviral/antibacterial defence in lower animals. In plants, the protein appears to have a protective effect against phytotoxic stresses, such as flooding, draught, too high or low temperature, salt stress or exposure to heavy metals. The finding for the latter stress condition is corroborated by earlier reports that TCTP levels are considerably up-regulated upon exposure of earthworms to high levels of heavy metals. Given the involvement of TCTP in many biological processes aimed at maintaining cellular or whole-body homeostasis, it is not surprising that dysregulation of TCTP levels may promote a range of disease processes, foremost cancer. Indeed a large body of evidence now supports a role of TCTP in at least the most predominant types of human cancers. Typically, this can be ascribed to both the anti-apoptotic activity of the protein and to its function in promoting cell growth and division. However, TCTP also appears to be involved in the later stages of cancer progression, such ...

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“…Toxins including hyaluronidase, proteases, low molecular mass insecticidal peptides, Translationally Controlled Tumor Protein (TCTP) and phospholipases-D have been identified [1], [2], [13], [14], [15], [16], [17].…”

Section: Introductionmentioning

confidence: 99%

A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization

et al. 2013

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Loxoscelism is the designation given to clinical symptoms evoked by Loxosceles spider's bites. Clinical manifestations include skin necrosis with gravitational spreading and systemic disturbs. The venom contains several enzymatic toxins. Herein, we describe the cloning, expression, refolding and biological evaluation of a novel brown spider protein characterized as a hyaluronidase. Employing a venom gland cDNA library, we cloned a hyaluronidase (1200 bp cDNA) that encodes for a signal peptide and a mature protein. Amino acid alignment revealed a structural relationship with members of hyaluronidase family, such as scorpion and snake species. Recombinant hyaluronidase was expressed as N-terminal His-tag fusion protein (∼45 kDa) in inclusion bodies and activity was achieved using refolding. Immunoblot analysis showed that antibodies that recognize the recombinant protein cross-reacted with hyaluronidase from whole venom as well as an anti-venom serum reacted with recombinant protein. Recombinant hyaluronidase was able to degrade purified hyaluronic acid (HA) and chondroitin sulfate (CS), while dermatan sulfate (DS) and heparan sulfate (HS) were not affected. Zymograph experiments resulted in ∼45 kDa lytic zones in hyaluronic acid (HA) and chondroitin sulfate (CS) substrates. Through in vivo experiments of dermonecrosis using rabbit skin, the recombinant hyaluronidase was shown to increase the dermonecrotic effect produced by recombinant dermonecrotic toxin from L. intermedia venom (LiRecDT1). These data support the hypothesis that hyaluronidase is a “spreading factor”. Recombinant hyaluronidase provides a useful tool for biotechnological ends. We propose the name Dietrich's Hyaluronidase for this enzyme, in honor of Professor Carl Peter von Dietrich, who dedicated his life to studying proteoglycans and glycosaminoglycans.

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Molecular cloning, heterologous expression and functional characterization of a novel translationally-controlled tumor protein (TCTP) family member from Loxosceles intermedia (brown spider) venom

Cited by 44 publications

References 56 publications

Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones

Tissue-Specific Venom Composition and Differential Gene Expression in Sea Anemones

The Translational Controlled Tumour Protein TCTP: Biological Functions and Regulation

A Novel Hyaluronidase from Brown Spider (Loxosceles intermedia) Venom (Dietrich's Hyaluronidase): From Cloning to Functional Characterization

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