Spider Ecophysiology || Main Components of Spider Venoms

Chapter 14

Main Components of Spider Venoms

Wolfgang Nentwig and Lucia Kuhn-Nentwig

14.1 Introduction

Venomglands are already present in the oldest spider group, theMesothelae. The glands

lie in the anterior portion of the cheliceral basal segment but are very small, and it is

doubtful how much the venom contributes to the predatory success. In mygalomorph

spiders, the well-developed venom glands are still in the basal segment of the chelicerae

and produce powerful venom that is injected via the cheliceral fangs into a victim. In all

other spiders (Araneomorphae), the venom glands have become much larger and reach

into the prosoma where they can take up a considerable proportion of this body part.

Only a few spiders have reduced their venom glands, either partially or completely

(Uloboridae, Holarchaeidae and Symphytognathidae are usually mentioned) or

modified them significantly (Scytodidae, see Suter and Stratton 2013).

As well as using venom, spiders may also use their chelicerae to overwhelm an

item of prey. It is primarily a question of size whether a spider chews up small

arthropods without applying venom or if it injects venom first. Very small and/or

defenceless arthropods are picked up and crashed with the chelicerae, while larger,

dangerous or well-defended items are carefully approached and only attacked with

venom injection. Some spiders specialize on prey groups, such as noctuid moths

(several genera of bola spiders among Araneidae), web spiders (Mimetidae), ants

(Zodarion species in Zodariidae, aphantochiline thomisids, several genera among

Theridiidae, Salticidae, Clubionidae and Gnaphosidae) or termites (Ammoxenidae).

However, these more or less monophagous species amount only to roughly 2 % of all

known spider species, while 98 % are polyphagous. From these considerations, it

follows that the majority of spider venoms are not tailored to any given invertebrate

or insect group but are rather unspecialized to be effective over a broad spectrum of

prey types that spiders naturally encounter.

W. Nentwig (*) • L. Kuhn-Nentwig

Institute of Ecology and Evolution, University of Bern, Bern, Switzerland

e-mail: [email protected]

W. Nentwig (ed.), Spider Ecophysiology,DOI 10.1007/978-3-642-33989-9_14, # Springer-Verlag Berlin Heidelberg 2013

191

mailto:[email protected]

While so far none of the venoms from specialized spider species have been

investigated, we do have in the meantime a broad overview on the composition of

the venom of a few well-investigated species. According to recent reviews

(Vassilevski et al. 2009; Kuhn-Nentwig et al. 2011), six main groups of components

can be distinguished for spider venoms: low molecular mass compounds,

acylpolyamines, linear peptides, cysteine-rich mini-proteins, large proteins and

enzymes (Table 14.1).

14.2 Low Molecular Mass Compounds

Most scientists investigating spider venom focus on substances other than low

molecular mass compounds which are usually more a side result of research.

From what is known at present however, it can be stated that spider venoms contain

a vast variety of such compounds. They are comprised of organic acids, nucleotides

and nucleosides, amino acids, amines, polyamines and other substances, many of

them functioning as neurotransmitters.

Table 14.1 Main component categories and some characteristics from spider venoms

Venom

compound

category

Molecular

size (kDa) Function Distribution

Molecular

diversity

Low molecular

mass

compounds

<1 Various. Some are

neurotransmitters,

some support other

compounds

synergistically,

often unknown

Probably in all spider

venoms

Limited

Acylpolyamines <1 Neurotoxins, act on ion

channels

Main toxic category in

Araneidae and

Nephilidae, common

in Agelenidae, also

in a few further

families

Limited

Linear peptides 1–9 Destroy membranes Known form Lycosoidea

and Zodariidae,

probably also in a

few more families

High

Cysteine-rich

mini-

proteins

2–15 Neurotoxins, act on ion

channels

Known from most

families

Very high

Large proteins 110–140 Destroy membranes Theridiidae Potentially

high

(unknown)

Enzymes 18–44 Destroy membranes

and tissue

Probably in all spider

venoms, main

category in

Sicariidae

Limited

192 W. Nentwig and L. Kuhn-Nentwig

The venom cation concentrations of Cupiennius salei (Ctenidae) are 9 mM Na+,

215 mM K+ and 1 mM Ca2+. This is in contrast to the cation concentrations of its

haemolymph (about 200 mM Na+, 10 mM K+ and 4 mM Ca2+), meaning that the

potassium concentration in the venom is increased more than 20-fold, compared to

the haemolymph, and, respectively, the sodium concentration is decreased (Kuhn-

Nentwig et al. 1994). At such concentrations, potassium is able to induce depolari-

zation of excitable cell membranes, causing paralysis of a prey item. Potassium is

also known as an effective synergist of neurotoxins in Cupiennius salei(Wullschleger et al. 2004, 2005). There are no comparable data for other spiders

but we assume that such inverse ion concentrations are widespread among spiders.

Citric acid has been detected in 48 spider species from 16 families in

concentrations of 16–147 mM (Kuhn-Nentwig et al. 2011). There are several

reasons for its presence in spider venoms: it could prevent bacterial growth; it

could be part of the venom glands’ buffer system to compensate for highly cationic

cytolytic peptides and acylpolyamines; it could function as an enhancer to enforce

the effect of other substances or as a divalent metallic ion chelator; and finally it

could also contribute to a partial inhibition of zinc ion metalloproteases and Ca2+-

dependent enzymes (i.e. phospholipases A2) in venom glands. After injection into a

prey item, the high citric acid concentration would be diluted, thus activating the

enzymes (Odell et al. 1999). Further organic acids from spider venoms are lactic

acid and phosphoric acid.

Sulphated and other nucleosides are known from the venoms of 30 species from

11 families (Schroeder et al. 2008; Kuhn-Nentwig et al. 2011). In the venom of

several Loxosceles species (Sicariidae), these compounds are very common and

constitute even up to about 50 % of the venom total dry mass in the venom of the

agelenid Tegenaria agrestis (Taggi et al. 2004). These and related substances can

induce paralytic and also lethal effects in insects.

All biogenic amino acids have been identified from spider venoms. Taurine has

been detected in the venoms of Cupiennius salei and the black widow Latrodectustredecimguttatus (Theridiidae). Glutamate and GABA, several biogenic amines such

as histamine, tyramine, serotonin, octopamine, dopamine and 5-hydroxytryptamine

(5-HT; serotonin), as well as polyamines (spermine, spermidine, putrescine and

cadaverine), have also been identified from spider venoms. These substances influence

the nervous system of insects or act directly as neurotransmitters. Acetylcholine,

choline, noradrenaline and adrenaline are further neurotransmitters in the insect

nervous system which were also identified from several spider venoms (Rash and

Hodgson 2002; Schroeder et al. 2008).

Histamine is well known from bee and wasp venoms. In vertebrates it produces

pain and is therefore seen as a defensive substance (Bettini 1978). This “pain

theory” is not really convincing for spiders because only large spiders (Ctenidae,

Sparassidae, Theraphosidae) suffer from vertebrate predators, while for smaller

spiders, invertebrates are more important predators. In insects, histamine acts as a

neurotransmitter, targeting ionotropic receptor channels, i.e. it enhances synergisti-

cally the effect of mini-proteins that affect ion channels (Wullschleger et al. 2005).

14 Main Components of Spider Venoms 193

14.3 Acylpolyamines

Acylpolyamines are a class of neuroactive compounds, with a polyamine structure

that frequently contains an aromatic acyl end moiety (indolic or phenolic) at its end

(350–1,000 Da). A high structural diversity within these compounds is obtained by

a combination of different acyl groups with polyamine chains, varying in length,

number of amide bonds and functional groups. There are two groups of

acylpolyamine toxins; those containing amino acids and those not containing

them (Fig. 14.1). In a similar manner, they both provoke a reversible paralysis

caused by blocking activated postsynaptic glutamate receptor channels

(McCormick and Meinwald 1993; Schafer et al. 1994; Itagaki and Nakajima

2000). So far 176 different acylpolyamines have been identified from 20 species

in eight families (Kuhn-Nentwig et al. 2011), and such a high diversity of

compounds is seen as fulfilling the principles of combinatorial chemistry to opti-

mise binding to a high diversity of targets.

Amino acids containing acylpolyamines have so far only been found in the orb

weaver families Araneidae and Nephilidae. A total of 82 different toxins have been

described: 18 from six Araneus and Argiope species, 64 from three Nephila and twoNephilengys species (Itagaki et al. 1997; Palma et al. 1998; McCormick and

Meinwald 1993). Araneidae and Nephilidae are regarded as two separate but

closely related families that obviously developed amino acids containing

acylpolyamines as one of their main toxin groups. There are no acylpolyamines

records from other families in the superfamily Araneoidea, namely, none from

Tetragnathidae and Linyphiidae (see also Appendix, this volume).

Non-amino acids containing acylpolyamine toxins have been identified from

three mygalomorph families (Ctenizidae, Hexathelidae and Theraphosidae) and

three other families (Agelenidae, Amaurobiidae and Pisauridae), but not from

Araneoidea. In all families, only one to four different compounds per species

Fig. 14.1 Characteristic acylpolyamine toxins from spider venom. (a) Argiopine from Argiope lobata(Araneidae) as an example for an amino acid-containing acylpolyamines with phenolic end group and

(b) AGEL 489 from Agelenopsis aperta (Agelenidae) as an example for a non-amino acid-containing

acylpolyamines with an indolic end group. Adapted from Kuhn-Nentwig et al. (2011)


were found, but in both so far investigated agelenids, a much higher diversity was

found (Agelenopsis aperta 68 and Hololena curta 12 compounds) (Chesnov et al.

2001; Tzouros et al. 2005). In contrast to Araneidae and Nephilidae, these six

families primarily rely on other venom components, mainly mini-proteins. We

assume that non-amino acids containing acylpolyamine toxins may possibly be

much more widespread than it is known so far.

14.4 Linear Peptides

Linear peptides of diverse length and cationic charge have been identified in the

venom of some spider species. These peptides adopt an a-helical conformation and

are able to destroy prokaryotic and/or eukaryotic cell membranes (Kuhn-Nentwig

2003, 2009). Therefore, they have also been named cytolytic, membranolytic or

antimicrobial peptides, and because of their cationic charge, the term small cationic

peptides is also used. A few small linear peptides isolated so far only from the

ctenid Phoneutria nigriventer are exceptional by not adopting an a-helix.Linear peptides usually do not contain cysteine residues and have a higher

amount of lysines and arginines; thus, they have relatively high positive net charges

between +3 and +10. They are disordered in aqueous solutions, but adopt an

a-helical structure in the presence of negatively charged membranes. These basic

peptides are attracted to the cell surfaces by electrostatic interactions between their

positively charged side chains of lysine and arginine and negatively charged

membrane phospholipid headgroups and phosphate groups containing lipopolysac-

charides or teichoic acids of cellular membranes. Different membrane disrupting

models have been discussed, but what they do all have in common is that the

membrane is finally destroyed (Fig. 14.2).

The molecular mass range of these “short” peptides varies from 1,910 to

5,221 Da which corresponds to 18–48 amino acids. There are 72 records concerning

eight families and 17 species: 36 records from Cupiennius salei (Ctenidae), 12records from Lachesana tarabaevi (Zodariidae) and the remaining records from

lycosids, oxyopids and a few other families. Besides these short peptides, 16 further

“large” peptides have been reported for L. tarabaevi, composed of 69–75 amino

acid residues (7,880–8,571 Da) and with a net charge of +14. These peptides exhibit

two a-helical regions connected by a short sequence of four amino acids, and it is

assumed that two short peptides form the large peptide in a “head-to-tail” orienta-

tion. Their insecticidal effect is superior to the effects of the small peptides (Kozlov

et al. 2006; Vassilevski et al. 2008; Kuhn-Nentwig et al. 2011).

The cytolytic acting peptides from Cupiennius salei are grouped into several

cupiennin families; in Lachesana tarabaevi the short peptides are called latarcins,

the large cyto-insectotoxins. In both species, these peptides are very important in

the prey-killing process, see also Kuhn-Nentwig and Nentwig (2013). Nevertheless,

this action is supported by other venom components (low molecular mass

compounds, neurotoxic mini-proteins and enzymes). If these results can be


generalized to Ctenidae, Lycosidae, Oxyopidae and related families (Lycosoidea),

the development of cytolytic peptides could represent a new evolutionary step of

this group and of Zodariidae.

14.5 Mini-proteins

Mini-proteins comprise peptides with molecular masses between 2,650 and

14,800 Da with most toxins between 3,000 and 9,000 Da. They contain 6–14

cysteines (Table 14.2) and exert a typical complex pattern of disulphide bridges.

The most common pattern follows the “inhibitor cysteine knot” (ICK) motif,

exhibiting a spatial structure consisting of a b-hairpin and a “knot” built by the

C3–C6 bond penetrating the ring formed by the two other bonds and the involved

amino acids (Norton and Pallaghy 1998). In proteins with six cysteines, the

disulphide bridges are arranged as C1–C4, C2–C5 and C3–C6, and with eight

cysteines, the arrangement is C1–C4, C2–C5, C3–C8 and C6–C7 in which the

fourth disulphide bridge C6–C7 is introduced into the extended b-hairpin structure.Nearly 1,000 different mini-proteins are known so far from the venom of 60

spider species belonging to 20 families (Kuhn-Nentwig et al. 2011). This

characterizes mini-proteins as the most common venom compound in spiders,

probably occurring in the venoms of most spider families, and there appear to be

only a few families relying on other main components (see below). The increasing

number of transcriptomic studies indicates that many different mini-proteins occur

in one venom and more than one hundred different toxins or variations of a few

different toxin types are not uncommon in a single species (e.g. Tang et al. 2010;

Zhang et al. 2010).

Fig. 14.2 Amino acid sequences and three-dimensional structures of (a) short cationic a-helicalpeptides from the ctenid Cupiennius salei and (b) the zodariid Lachesana tarabaevi. Positivelycharged amino acids in the amino acid sequences are given in grey. In the spatial structure of the

peptides charged/polar residues are shown in black and hydrophobic amino acids in grey. TheProtein Data Bank codes are given in brackets. Adapted from Kuhn-Nentwig et al. (2011)


Mini-proteins act selectively against a specific target and form a tight and stable

toxin-target complex. They mainly act on membrane proteins in electro-excitable cell

membranes (neuronal and muscular cells), primarily modulating ion channels such as

calcium (Ca2+), sodium (Na+) and potassium (K+), but also on mechano-, chemo-,

and thermosensitive receptors, and inhibit, activate or delay voltage-activated

channels so that their normal ion regulation is affected (see Herzig and King 2013).

Usually, these toxins are already very effective at nanomolar concentrations, which is

at least one order of magnitude better than the average concentration needed for the

unspecific membrane destruction by cytolytic peptides.

The fast transport of impulses along and between excitable cells is caused by the

movement of sodium (Na+) ions across the membranes of excitable cells via

voltage-gated sodium (Nav) channels. These ion channels enable the coordination

of locomotion, and for this reason, they are usually the most abundant ion channels

in nerve and muscle tissue. This makes sodium channels also the first target for

paralytic neurotoxins. There is a high diversity in this family of sodium channels

made of at least nine members: Nav1.1 to Nav1.9. Depending on the precise mode of

action, three toxin types are distinguished: b-toxins shift the voltage dependence ofNav channels activation, d-toxins delay the inactivation of Nav channels and m-toxins inhibit Nav channels. About 40 % of all functionally characterized mini-

proteins are sodium channel inhibitors.

In most tissues of animals, especially in the nervous system and in muscles, calcium

channels regulate the release of neurotransmitters. They can be inhibited by toxins

causing a long-lasting specific blockade of these presynaptic voltage-gated calcium

(Cav) channels, typically called omega-toxins (o-toxins). There are six recognised

types and many subtypes of voltage-gated calcium channels (L, N, P, Q, R and T)

differing in their electrophysiological characteristics and reacting differently to differ-

ent inhibitors or activators (Rash and Hodgson 2002). In spider venoms, roughly 35 %

of all functionally characterized mini-proteins are calcium channel inhibitors.

Table 14.2 Frequency of the number of cysteines in mini-proteins with ICK motif for major

spider taxa (data from Kuhn-Nentwig et al. 2011)

Number of toxins recorded per given number of cysteines

6 7 8 9 10 11 12 14

Hexathelidae 61 1 18 8

Theraphosidae 122 4 27 5 1

Other mygalomorphs 2 1 8

Haplogynae 1 14 12 7

Agelenidae 28 2 25 2 7

Amaurobiidae 4

Sparassidae 7

Ctenidae 14 7 25 7 14 2 8

Lycosidae 9 111 8 18 1 5 6

Oxyopidae 3

% of peptides 38.2 4.1 39.2 2.4 10.1 0.7 4.4 1.0


Potassium channels comprise a highly diverse and large group of ion channels,

regulating different cellular processes in the body. Voltage-gated potassium (Kv)

channels consist of four main subunits and several accessory subunits to form an ion

pore. Spider k-toxins inhibit voltage-activated potassium channels and account for

25 % of all functionally characterized mini-proteins.

14.6 Large Proteins

The largest compounds in spider venom are proteins with a molecular mass

between 110 and 140 kDa. They have so far been found exclusively in the genera

Latrodectus (black widows), Steatoda and Achaearanea (Theridiidae).

Investigations into the venom of Latrodectus species concern primarily the North

American L. mactans, the Eurasian L. tredecimguttatus and the Australian L.

hasselti. In all cases, the venom consists of seven major proteins selectively toxic

to three groups: (1) a-latrotoxin (a-LTX) which is vertebrate selective and has a

molecular mass of 130 kDa; (2) five latroinsectotoxins (LIT), namely, a-, b-, g-, d-,and e�-LIT, which are selective for insects and have a molecular mass between 110

and 140 kDa; and (3) the 120 kDa a-latrocrustotoxin (a-LTX) which is selective forcrustaceans (Grishin 1998). These masses correspond to 1,000–1,200 amino acid

residues with a rather high level of homology of over 30 % residue identity

(Vassilevski et al. 2009).

a-LTX has a high affinity to form dimers that aggregate into tetramers and then

insert into the lipid membrane of nerve cells, thus forming a central channel. This

pore acts as a nonselective cation channel allowing a massive influx of extracellular

Ca2+ into the nerve, which leads to vesicular exocytosis (Rohou et al. 2007). In

other words, this represents an exhaustive neurotransmitter release from a variety of

nerves that depletes the synaptic vesicles, blocks the signal transmission and causes

muscular paralysis. a-LTX causes secretion of all known neurotransmitter types

and the effects of latroinsectotoxins and latrocrustotoxin are rather similar. The

highly toxic effect of the Latrodectus toxins is enhanced by an 8 kDa peptide that isnot toxic and cannot form membrane pores by itself, but augments the affinity of a-LTX to membranes (Kiyatkin et al. 1995).

14.7 Enzymes

A variety of enzymes have been identified in spider venoms from 49 species,

belonging to 14 families (Kuhn-Nentwig et al. 2011). Most of these enzymes can

be separated into two groups, one that cleaves polymers in the extracellular matrix,

and the other one targeting phospholipids and related compounds in membranes.

The overall purpose of a co-injection of enzymes with toxins into a prey’s tissue is

obvious: by destroying the barrier of extracellular matrix and cell membranes, the


toxins can reach their targets faster. Additionally, the proteolytic activity of some of

these enzymes may facilitate the subsequent preoral digestion.

Hyaluronidases, historically the first enzymes found in spider venoms, cleave the

mucopolysaccharide hyaluronan (hyaluronic acid), a major constituent of the extra-

cellular matrix. This facilitates the spread of toxins and further venomous

compounds, and therefore it has been frequently termed “spreading factor” (e.g.

Bettini 1978). Hyaluronidases differ slightly between spider species since their

apparent molecular mass varies between 32 and 44 kDa. A second major group of

enzymes targeting the extracellular matrix is collagenases. These are matrix

metalloproteases, cleaving peptide bonds between proline and other amino acid

residues in collagen, a key compound in the animal extracellular matrix.

Cell membranes of living organisms consist of a lipid bilayer that is mainly

composed of phospholipids. Inner and outer surfaces differ in chemical composi-

tion with phosphatidylcholine, sphingomyelin and a variety of glycolipids deter-

mining the outer surface. These molecules are the targets of various hydrolase

enzymes breaking down the phosphodiester bond (phosphodiesterase), degrading

sphingomyelin (sphingomyelin phosphodiesterase or sphingomyelinase D) or

hydrolysing phospholipids (phospholipases). Since sphingomyelinase D also

hydrolyses lysoglycerophospholipids or lysophosphatic acid, it is now usually

called phospholipase D. Phospholipase D became a famous case among spider

venom enzymes because sicariids are the spider family relying to the highest degree

on the activity of these enzymes when subduing a prey (Binford et al. 2009; see also

Binford 2013). Loxosceles venom is very potent, and due to its enzymatic nature, it

is the only venom which causes necrotic effects in humans.

It is obviously very efficient to support the effect of neurotoxic components by

enzymes which facilitate spreading. So far, enzymes targeting the extracellular

matrix or membrane compounds have only been found in a few spider species, but

we assume that it is much more common in spider venoms.

14.8 Evolutionary Strategies of Spider Venom

Spiders possess venom glands to produce venom that they use primarily to paralyse

and /or kill their prey items. The main strategy to reach these goals seems to rely

mainly on mini-proteins. Most spiders investigated so far possess a variety of mini-

proteins in their venom glands. It is, however, difficult to decide whether mini-

proteins or low molecular mass compounds represent the plesiomorphic repertoire

of all spiders, since we have no information on the venom composition of the most

plesiomorphic spider group (Mesothelae).

Unfortunately, we still have only very limited knowledge on spider venoms,

derived from some 0.4 % of all known spider species, belonging to less than one

third of the known families. This research bias was driven by a selection towards

large and easily accessible spiders and species of medical importance, while other

important and large groups were completely neglected. At this stage, generalisations

are risky but some general trends are nevertheless observable.


Since the venoms frommany mygalomorph species contain many mini-proteins, a

variety of low molecular mass compounds and enzymes, we assume that early in the

evolution of spider venoms, this turned out to be a very well-functioning and reliable

mixture. Nevertheless, numerous modifications, changes and replacements have

occurred, which we summarise here as three main lines of evolutionary change:

1. Mini-proteins are permanently modified. Structurally, mini-proteins can be

considered superficially as similar peptides, most of them in the range of

3–8 kDa. However, the variation of only a few features such as molecular target

(functional diversity), sequence variations, number of cysteines or size (struc-

tural diversity) yields a nearly endless number of different toxins. In many spider

species, dozens of mini-proteins occur and the record so far consists of 166 mini-

proteins known from one peptidomic study on the theraphosid Haplopelmahainanum (Tang et al. 2010). Quite often, the difference between the structures

of two peptides consists only in an exchange of one amino acid, which can result

in drastic changes of potency and/or selectivity.

2. Supporting mechanisms or synergisms between mini-proteins and other

components, namely, low molecular mass compounds, linear peptides and

enzymes, frequently increase their effect. This can be achieved either by directly

attacking neuronal or muscular cells or by destroying their membranes or target

tissue so that mini-proteins have easier access to their targets. The first may be

achieved by a variety of neurotransmitters and further neuroactive compounds,

the latter by linear peptides or enzymes. This enables the spider to inject less

venom to get the same result, suggesting that energetic reasons are the main

driver (Wullschleger et al. 2004, 2005).

3. If mini-proteins can be substituted by something better, it is obvious that they

should be replaced, partially or completely. There are at least three examples of

spider groups where mini-proteins have been more or less completely replaced

by “better” compounds. The first is given by Araneidae and Nephilidae, relying

mainly or exclusively on amino acids containing acylpolyamines. A second

example concerns Theridiidae which replaced mini-proteins by large neurotoxic

proteins. Thirdly, the venom of sicariids contains predominantly a highly effec-

tive phospholipase D. Also the increasing appearance of linear peptides in

ctenids and some related families (Lycosoidea) can be interpreted as an

approach of substituting venom components by such cytolytic peptides.

These changes and modifications are part of the evolutionary arms race to

optimize the venom composition permanently, but they also pose the question as

to which kind of venom may be “better”. Since the amount of venom needed to

subdue a given prey item is a crucial factor, comparative biotests may give an

answer. Tests with 14 spider species from 12 families showed that the LD50 for the

cockroach Blatta orientalis varies between 0.3 and 542 ng dry venom/mg insects,

i.e. over more than three orders of magnitude. The best results, however, were

achieved from venoms with very different venom strategies (the theraphosid

Avicularia metallica with mini-proteins, the sicariid Loxosceles deserta with phos-

pholipase D and the theridiid Latrodectus hesperus with large neurotoxic proteins)


and varied in a much smaller range between 0.9 and 10 ng dry venom/mg insect

(Friedel and Nentwig 1989; Nentwig et al. 1992). This indicates that different main

classes of spider venom components can be more or less equally toxic and success-

ful, but the variation within venom components or spider families is much larger.

14.9 Conclusions

Spider venoms contain a huge diversity of compounds that can be classified into six

major categories: low molecular mass compounds, acylpolyamines, linear cationic

peptides, cysteine-rich mini-proteins, large neurotoxic proteins and enzymes. The

venoms frommanymygalomorph species, containing several mini-proteins, a variety

of low molecular mass compounds and enzymes, represent a very well-functioning

and reliable mixture and may be seen as the basic form of spider venoms. Neverthe-

less, numerous modifications, changes and replacements have occurred. At least three

spider groups developed very different venom compositions: Araneidae and

Nephilidae rely mainly on amino acids containing acylpolyamines, Theridiidae

have developed large neurotoxic proteins and Sicariidae venoms predominantly

contain phospholipase D.

References

Bettini S (1978) Arthropod venoms. Handbook of experimental pharmacology. Springer, Berlin

Binford G (2013) The evolution of a toxic enzyme in Sicariid spiders. In: Nentwig W (ed) Spider

ecophysiology. Springer, Heidelberg (this volume)

Binford GJ, Bodner MR, Cordes MH, Baldwin KL, Rynerson MR, Burns SN, Zobel-Thropp PA

(2009) Molecular evolution, functional variation, and proposed nomenclature of the gene

family that includes sphingomyelinase D in sicariid spider venoms. Mol Biol Evol 26:547–566

Chesnov S, Bigler L, Hesse M (2001) The acylpolyamines from the venom of the spider

Agelenopsis aperta. Helv Chim Acta 84:2178–2197

Friedel T, Nentwig W (1989) Immobilizing and lethal effects of spider venoms on the cockroach

and the common mealbeetle. Toxicon 27:305–316

Grishin EV (1998) Black widow spider toxins: the present and the future. Toxicon 36:1693–1701

Herzig V, King G (2013) The neurotoxic mode of action of venoms from the spider family

Theraphosidae. In: Nentwig W (ed) Spider ecophysiology. Springer, Heidelberg (this volume)

Itagaki Y, Nakajima T (2000) Acylpolyamines: mass spectrometric analytical methods for

Araneidae spider acylpolyamines. J Toxicol Toxin Rev 19:23–52

Itagaki Y, Fujita T, Naoki H, Yasuhara T, Andriantsiferana M, Nakajima T (1997) Detection of

new spider toxins from a Nephilengys borbonica venom gland using on-line m-column HPLC

continuous flow (FRIT) FAB LC/MS and MS/MS. Nat Toxins 5:1–13

Kiyatkin NI, Kulikovskaya IM, Grishin EV, Beadle DJ, King LA (1995) Functional characteriza-

tion of black widow spider neurotoxins synthesised in insect cells. Eur J Biochem 230:854–859

Kozlov SA, Vassilevski AA, Feofanov AV, Surovoy AY, Karpunin DV, Grishin EV (2006)

Latarcins, antimicrobial and cytolytic peptides from the venom of the spider Lachesanatarabaevi (Zodariidae) that exemplify biomolecular diversity. J Biol Chem 281:20983–20992

Kuhn-Nentwig L (2003) Antimicrobial and cytolytic peptides of venomous arthropods. Cell Mol

Life Sci 60:2651–2668


Kuhn-Nentwig L (2009) Cytolytic and antimicrobial peptides in the venom of scorpions and

spiders. In: de Lima ME (ed) Animal toxins: state of the art. Editora UFMG, Belo Horizonte

Kuhn-Nentwig L, Nentwig W (2013) The cytotoxic mode of action of the venom of Cupienniussalei (Ctenidae). In: NentwigW (ed) Spider ecophysiology. Springer, Heidelberg (this volume)

Kuhn-Nentwig L, Schaller J, Nentwig W (1994) Purification of toxic peptides and the amino acid

sequence of CSTX-1 from the multicomponent venom of Cupiennius salei (Araneae:

Ctenidae). Toxicon 32:287–302

Kuhn-Nentwig L, Stocklin R, Nentwig W (2011) Venom composition and strategies in spiders:

is everything possible? Adv Insect Physiol 40:1–86

McCormick KD, Meinwald J (1993) Neurotoxic acylpolyamines from spider venoms. J Chem

Ecol 19:2411–2451

Nentwig W, Friedel T, Manhart C (1992) Comparative investigations on the effect of the venom of

18 spider species onto the cockroach Blatta orientalis (Blattodea). Zool Jb Physiol 96:279–290Norton RS, Pallaghy PK (1998) The cystine knot structure of ion channel toxins and related

polypeptides. Toxicon 36:1573–1583

Odell GV, Fenton AW, Ownby CL, Doss MP, Schmidt JO (1999) The role of venom citrate.

Toxicon 37:407–409

Palma MS, Itagaki Y, Fujita T, Naoki H, Nakajima T (1998) Structural characterization of a new

acylpolyaminetoxin from the venom of Brazilian garden spider Nephilengys cruentata.Toxicon 36:485–493

Rash LD, Hodgson WC (2002) Pharmacology and biochemistry of spider venoms. Toxicon 40:

225–254

Rohou A, Nield J, Ushkaryov YA (2007) Insecticidal toxins from black widow spider venom.

Toxicon 49:531–549

Schafer A, Benz H, Fiedler W, Guggisberg A, Bienz S, Hesse M (1994) Polyamine toxins from

spiders and wasps. In: Cordell GA, Brossi A (eds) The alkaloids, chemistry and pharmacology.

Academic, San Diego

Schroeder FC, Taggi AE, Gronquist M, Malik RU, Grant JB, Eisner T, Meinwald J (2008) NMR-

spectroscopic screening of spider venom reveals sulfated nucleosides as major components for

the brown recluse and related species. Proc Natl Acad Sci USA 105:14283–14287

Suter RB, Stratton GE (2013) Predation by spitting spiders—elaborate venom gland, intricate

delivery system. In: Nentwig W (ed) Spider ecophysiology. Springer, Heidelberg (this volume)

Taggi AE, Meinwald J, Schroeder FC (2004) A new approach to natural products discovery

exemplified by the identification of sulfated nucleosides in spider venom. J Am Chem Soc

126: 10364–10369

Tang X, Zhang Y, Hu W, Xu D, Tao H, Yang X, Li Y, Jiang L, Liang S (2010) Molecular

diversification of peptide toxins from the tarantula Haplopelma hainanum (Ornithoctonushainana) venom based on transcriptomic, peptidomic, and genomic analyses. J Proteome

Res 9:2550–2564

Tzouros M, Chesnov S, Bienz S, Hesse M, Bigler L (2005) New linear polyamine derivatives in

spider venoms. Toxicon 46:350–354

Vassilevski AA, Kozlov SA, Samsonova OV, Egorova NS, Karpunin DV, Pluzhnikov KA,

Feofanov AV, Grishin EV (2008) Cyto-insectotoxins, a novel class of cytolytic and insecticidal

peptides from spider venom. Biochem J 411:687–696

Vassilevski AA, Kozlov SA, Grishin EV (2009)Molecular diversity of spider venom. Biochemistry

(Moscow) 74:1505–1534

Wullschleger B, Kuhn-Nentwig L, Tromp J, Kampfer U, Schaller J, Schurch S, Nentwig W (2004)

CSTX-13, a highly synergistically acting two-chain neurotoxic enhancer in the venom of the

spider Cupiennius salei (Ctenidae). Proc Natl Acad Sci USA 101:11251–11256

Wullschleger B, Nentwig W, Kuhn-Nentwig L (2005) Spider venom: enhancement of venom efficacy

mediated by different synergistic strategies in Cupiennius salei. J Exp Biol 208:2115–2121

Zhang Y, Chen J, Tang X, Wang F, Jiang L, Xiong X, Wang M, Rong M, Liu Z, Liang S (2010)

Transcriptome analysis of the venom glands of the Chinese wolf spider Lycosa singoriensis.Zoology (Jena) 113:10–18


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Spider Ecophysiology || Main Components of Spider Venoms