Presynaptic neurotoxin that causes massive release of neurotransmitters from vertebrate (but not invertebrate) nerve terminals and endocrine cells via a complex mechanism involving activation of receptor(s) and toxin insertion into the plasma membrane with subsequent pore formation. Binds to neurexin-1-alpha (NRXN1) in a calcium dependent manner, adhesion G protein-coupled receptor L1 (ADGRL1, also termed latrophilin-1 and calcium-independent receptor of latrotoxin (CIRL)), and receptor-type tyrosine-protein phosphatase S (PTPRS), also termed PTP sigma (PubMed:7592578, PubMed:8798521, PubMed:12110683). NRXN1 and PTPRS are suggested to provide a platform for binding and subsequent pore formation events (PubMed:9799228, PubMed:11572875). In contrast, binding to ADGRL1 does not involve oligomerization and channel formation, but direct downstream stimulation of the synaptic fusion machinery (PubMed:12764091). Homotetramer in membranes. Forms a membrane channel in the prey. Expressed in venom gland, cephalothorax, and abdomen tissues from both males and females. Expressed in all life stages examined, including adults, spiderlings and eggs. The H8 helix is predicted to insert into membranes and form pores by assembling into tetramers. The helix is contained within a helical bundle domain that undergoes significant conformational changes during pore formation to allow exposure of the H8 transmembrane helix and transition of the toxin from a soluble monomer to a transmembrane tetramer. Processed by furin-like proteases at both the N- and C-termini. LD(50)is 20 ug/kg by subcutaneous injection into mice. Is an essentiel tool for stimulating exocytosis and study its mechanisms. Its mutant LTXN4C, which is unable to insert into membranes and form pores, plays a key role in understanding the dual mode of action of the wild-type toxin. May be used to antagonize botulinum neurotoxin poisoning and attenuate the neuromuscular paralysis via synapse remodeling. Is the main neurotoxin responsible for the human envenomation syndrome known as latrodectism that results from bites by Latrodectus species. Anti-alpha-LTX monoclonal antibody 4C4.1 blocks neurotransmitter release induced by this protein by preventing tetramerization and ionophore activity once inserted into cell membranes. However, 4C4.1 is incapable of reversing pore formation (PubMed:11086220). Belongs to the cationic peptide 01 (latrotoxin) family. 03 (alpha-latrotoxin) subfamily.