Vanillotoxins (VaTxs, subtypes VaTx1, VaTx2, and VaTx3) are

neurotoxins Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insultsSpencer 2000 that can adversely affect function in both developing and mature nerv ...

found in the venom of the

tarantula Tarantulas comprise a group of large and often hairy spiders of the family Theraphosidae. , 1,040 species have been identified, with 156 genera. The term "tarantula" is usually used to describe members of the family Theraphosidae, although m ...

'' Psalmopoeus cambridgei''. They act as

agonists An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the agon ...

for the

transient receptor potential cation channel Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TR ...

subfamily V member 1 (

TRPV1 The transient receptor potential cation channel subfamily V member 1 (TrpV1), also known as the capsaicin receptor and the vanilloid receptor 1, is a protein that, in humans, is encoded by the ''TRPV1'' gene. It was the first isolated member of th ...

), activating the pain sensory system. VaTx1 and 2 also act as antagonists for the K_v2-type voltage-gated potassium channel ( K_v2), inducing paralytic behavior in small animals.

Origin

''P. cambridgei'', a tarantula from

Trinidad Trinidad is the larger and more populous of the two major islands of Trinidad and Tobago. The island lies off the northeastern coast of Venezuela and sits on the continental shelf of South America. It is often referred to as the southernmos ...

, uses its venom to paralyze its prey. Amongst other compounds, this venom contains all three subtypes of VaTxs: VaTx1, VaTx2, and VaTx3. The name of the toxin was derived from the vanilloid receptor TRPV1, to which the VaTxs bind.

Chemistry

Vanillotoxins have close homology to other

inhibitor cystine knot An inhibitor cystine knot (aka ICK or Knottin) is a protein structural motif containing three disulfide bridges. Knottins are one of three folds in the cystine knot motif; the other closely related knots are the Growth Factor Cystine Knot (GFCK) ...

(ICK) toxins. ICK toxins are best known as blockers of cation channels. The exact structure of the VaTxs has not yet been deduced, although some preliminary models have been proposed. VaTxs are 53-82% identical in amino acid sequence. VaTx1 and VaTx2 have an almost identical structure, while VaTx3 shows some diversity in its extruding protein loop.

Targets

All three subtypes of VaTxs act as agonists for TRPV1.

EC50 ] Half maximal effective concentration (EC50) is a measure of the concentration of a drug, antibody or toxicant which induces a Stimulus%E2%80%93response_model, response halfway between the baseline and maximum after a specified exposure time. Mo ...

of VaTx1, VaTx2, and VaTx3 for heterologously expressed TRPV1 channels is around 12, 2.5 and 0.3 μM, respectively. VaTx1 and VaTx2 also bind to the KCNIP2, K_v2 channel, although VaTx2 with a lower affinity than VaTx1. VaTx2 becomes effective on Kv2 at a minimal concentration of 40 μM.

Mode of action

In humans, the effect of VaTxs has not been systematically studied. In general, the venom of ''P. cambridgei'' is known to produce pain, but the amount of toxin that is present in a bite is too low to cause serious health problems . The effects of VaTxs on TRPV1 and K_v2 have been studied by injecting VaTxs subcutaneously in mice. VaTxs bind to the extracellular pore domain of TRPV1 in the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brai ...

causing the opening of the pore and cation influx, therefore triggering the activation of the pain system. Despite the similar architecture of TRPV1 and K_v2, VaTx1 and VaTx2 bind to the voltage-sensing domain of K_v2 rather than the pore-domain. By doing so, they increase the action potential threshold in the

neuromuscular junction A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation ...

, eliciting paralytic behavior.

References

{{Neurotoxins Ion channel toxins Spider toxins Neurotoxins