Neuronal receptors for phospholipases A(2 )and beta-neurotoxicity.
Some phospholipases A(2) interrupt neuromuscular communication by blocking the release of neurotransmitter into the synaptic cleft. Despite numerous studies, the molecular mechanism of their action is still largely obscure. In this review the best-characterized receptors for beta-neurotoxins are presented. We propose a model which could be useful in investigating the apparent inconsistency between the observed heterogeneity in the neuronal binding of beta-neurotoxins and the very similar pathomorphological and electrophysiological effects which they produce in the intoxicated tissue. We assume that beta-neurotoxins enter the nerve ending to exert their toxic effect. The model involves different pathways for phospholipase A(2) neurotoxins to reach the site of action inside the neuron, their respective extra- and intracellular neuronal receptors being key features of the pathway. Once in the nerve cell, beta-neurotoxins impair the function of the synaptic vesicles by phospholipid hydrolysis of the inner leaflet of the vesicle bilayer. The proportion of the products of the phospholipid hydrolysis, lysophospholipids and phospholipids in the membrane, has been demonstrated to be very important for the shaping of the membrane, affecting its fusogenic properties. Due to the same final step in the action of beta-neurotoxins, phospholipid hydrolysis, the consequences of their poisoning are practically identical.
Krizaj
I
I
Department of Biochemistry and Molecular Biology, Jozef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia. igor.krizaj@ijs.si
Gubensek
F
F
D000818:Animals; D004705:Endocytosis / Q000187:drug effects; D005089:Exocytosis / Q000187:drug effects; D008954:Models, Biological; D009411:Nerve Endings / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D009498:Neurotoxins; D018377:Neurotransmitter Agents; D010741:Phospholipases A