Author/Editor		Pungerčar, Jože; Vučemilo, Nataša; Faure, Grazyna; Bon, Cassian; Verheij, Hubertus M; Gubenšek, Franc; Križaj, Igor
Title		Ammodytin L, an inactive phospholipase A2 homologue with myotoxicity in mice, binds to the presynaptic acceptor of the beta-neurotoxic ammodytoxin C in torpedo: an indication for a phospholipase A2 activity-independent mechanism of action of beta-neurotoxins in fish?
Type		članek
Source		Biochem Biophys Res Commun
Vol. and No.		Letnik 244, št. 2
Publication year		1998
Volume		str. 514-8
Language		eng
Abstract		A Ser48 phospholipase A2-homologue, ammodytin L, which is myotoxic in mammals and devoid of any phospholipase A2 activity, completely inhibits the specific binding of the neurotoxic phospholipase A2, ammodytoxin C, to fish presynaptic membranes from Torpedo marmorata electric organ. In cross-linking experiments, 125I-ammodytin L labels the same membrane proteins as 125I-ammodytoxin C (70, 38.5-57.4 and 19.7 kDa). The formation of these adducts is completely prevented by the presenc eof ommadytoxin C but not of a non-toxic phospholipase A2, ammodytin I2. A chimeric phospholipase A2, constructed by associating the N-terminal half of ammodytoxin to the C-terminal half of ammodytin L, possesses a low, but significant phospholipase A2 activity, however it is not toxic to mice, probably due to abolition of the specific neuronal acceptor binding in mammals. Nevertheless, the chimeric phospholipase A2 is able to interact with the ammodytoxin acceptor in Torpedo marmorat electric organ. The existence of neuronal acceptors for ammodytin L and for the chimeric phospholipase A2 suggests that they may act as neurotoxins in fish. As ammodytin L does not posses any enzymatic activity it, therefore, appears to be an wxcellent tool to investigate the mechanism of action of beta-neurotoxins indepedently of their phospholipase A2 activity.
Descriptors		NEUROTOXINS RECEPTORS, PRESYNAPTIC VIPER VENOMS PHOSPHOLIPASES A MICE AMINO ACID SEQUENCE BASE SEQUENCE CHIMERIC PROTEINS DNA PRIMERS ELECTRIC ORGAN FISHES MICE NEUROMUSCULAR JUNCTION POLYMERASE CHAIN REACTION