Excitatory Neurotoxin: α-Latrotoxin

Introduction to α-Latrotoxin

Black widow spider α-latrotoxin, a member of the GTP-binding protein-coupled receptors (GPCRs) family, is a large protein with a size of about 120kDa. In general, α-latrotoxin consists of an N-terminal signal peptide (SP) domain, a conserved cysteine residues domain, a 22 ankyrin repeats domain, as well as a C-terminal domain. Among them, this conserved cysteine residues domain also contains two hydrophobic sequences that distribute across the cell membrane and fold in the nucleus of the α-latrotoxin. Nowadays, α-latrotoxin has been regarded as a powerful tool for revealing the mechanism of synaptic transmission in neurosciences. α-Latrotoxin can bind to its receptors on the presynaptic nerve terminals to further trigger the release of neurotransmitters by stimulating synaptic vesicle exocytosis.

Mechanism of Action of α-Latrotoxin

In the past few years of studies, the key role of α-latrotoxin in mediating the release of neurotransmitters and hormones have been confirmed in various types of cells, such as neuromuscular junctions, PC12 cell, pancreatic β-cells, neurohypophysis cells, and hormone-secreting cells. Moreover, pilot studies have suggested that high toxin concentration (>10 nM) of α-latrotoxin mainly induces the release of neurotransmitters by controlling the different functions of presynaptic structural elements. Another important ability of α-latrotoxin is to regulate Ca²⁺-independent neurotransmitter release. For instance, in the presence of calcium, α-latrotoxin inhibits the release of acetylcholine at the neuromuscular junction, and this inhibition disappears when calcium is removed. Numerous data have indicated that calcium controls the function of α-latrotoxin by regulating endocytosis in the nerves.

Receptors for α-Latrotoxin

Commonly, α-latrotoxin requires bind to specific receptors for stimulating neurosecretion in humans. Up to now, two groups of α-latrotoxin receptors, including Ca²⁺ dependent and Ca²⁺ independent receptors, have been purified and identified in the active zone of the presynaptic plasma membrane. Neurexins have been treated as typical Ca²⁺-dependent receptors that can bind to α-latrotoxin with high affinity. Also, CIRL/latrophilin has been considered as Ca²⁺-independent receptors for α-latrotoxin. Recent reports have shown that α-latrotoxin can bind with the intracellular G-protein signal region of CIRL/latrophilin for triggering the activation of exocytosis in vivo.

By continuing to grow in response to the requirements of our clients, Creative Biolabs is dedicated to exploring α-latrotoxin-induced studies in the nervous system to offer the most comprehensive, integrated solutions. If you are interested in our services, please contact us to discuss your project.