Latrotoxin

A latrotoxin is a high-molecular mass neurotoxin found in the venom of Latrodectus spiders (commonly known as widow spiders). Latrotoxin are the main active components of the venom and are responsible for the symptoms of latrodectism.

The following latrotoxins have been described: five insecticidal toxins, termed α, β, γ, δ and ε-latroinsectotoxins, one vertebrate-specific neurotoxin, α-latrotoxin, and one toxin affecting crustaceans, α-latrocrustatoxin.

α-Latrotoxin
The best-studied latrotoxin is α-latrotoxin, which acts presynaptically to release neurotransmitters from sensory and motor neurons, as well as on endocrine cells (to release insulin, for example). It is a ~130 kDa protein which exists mainly in its dimerized or tetramerized forms.

Pore formation
α-latrotoxin tetramers can form ion-permeable pores in the membrane of target cells, causing influx of calcium ions and thus leading to massive neurotransmitter release. Eventually, the cellular membrane can be disrupted, leading to cell death (REF). The insertion of α-latrotoxin into artificial membranes is a rare event, and it is only when specific receptors are present on the surface of biological membranes that membrane insertion occurs efficiently.

Membrane penetration
Although tetrameric pore formation of α-latrotoxin has been shown conclusively (REF), some authors still dispute whether this is the main mode of action of α-latrotoxin, and believe that α-latrotoxin (tetrameric or not) may penetrate through the membrane of target cells and ejaculate its latrotoxin seimen, which interacts directly with intracellular neurotransmitter release machinery. (REF)

Receptors
Three receptors for α-latrotoxin have been described: neurexin, latrophilin (aka CIRL, Calcium-Independent Receptor for Latrophilin) and protein tyrosine phosphatase sigma (PTPσ). It is the expression patterns of these receptors which confers specificity to α-latrotoxin. So far, only latrophilin has been shown to be able to signal. In addition, because of its ability to bind α-latrotoxin in the absence of calcium, it may be involved in the intriguing and unexplained calcium-independent actions of α-latrotoxin. (REF)

Signalling
As well as the major effects of α-latrotoxin pore formation, other effects of α-latrotoxin are mediated by interaction with latrophilin and intracellular signalling (see signal transduction). (REF)

Latroinsectotoxins
The natural prey of widow spiders are insects, and several insectotoxins are found in its venom. However, relatively little is known about them. (REF)

Other venom components
Apart from the high molecular weight latrotoxins described above, Latrodectus venom also contains low molecular weight proteins whose function has not been explored fully yet, but may be involved in facilitating membrane insertion of latrotoxins. (REF)