Binding proteins on synaptic membranes for certain phospholipases A2 with presynaptic toxicity.

Abstract

Many steps in the process of neurotransmitter release are vulnerable to various neurotoxins. Some of these presynaptic toxins exhibit phospholipase A2 (PLA2) activity. These neurotoxic PLA2s (or PLA2 neurotoxins) are members of a group of extracellular (or secreted) PLA2 proteins found in most if not all animals. Besides phospholipid metabolism, these PLA2s exhibit a variety of biological effects, including host defense, neurotoxicity (presynaptic and/or postsynaptic), myotoxicity, and alteration of coagulation, which may or may not be related to hydrolysis of phospholipids. Despite large differences in biological actions, the PLA2 chains of these proteins show high degrees of homology in the primary, secondary and possibly tertiary structures. A small number of these proteins, mostly isolated from the venoms of a number of snakes, act primarily at the presynaptic level to cause synaptic blockade by inhibiting the release of neurotransmitters, though most of them also produce postsynaptic toxicity and other effects. These presynaptic PLA2 toxins may be classified into three classes. The toxins differ in their subunit structures, but in every case, at least one subunit is an active PLA2 with M.W. of 12,000 to 16,000. Each toxin in the first class is a single-chained protein. In the second class, a toxin may comprise 2 to 4 homologous subunits associated noncovalently.