α-Latrotoxin and glycerotoxin differ in target specificity and in the mechanism of their neurotransmitter releasing action

L. Madeddu, J. Meldolesi, T. Pozzan, L. E Cardona Sanclemente, C. Bon

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

α-Latrotoxin, a high molecular weight protein (130,000) purified from the venom of the black widow spider, and a partially purified neurotoxin, glycerotoxin, prepared from extracts of the jaw glands of the polichaete annelid Glycera convoluta, were previously found to induce similar effects (stimulation of quantal acetylcholine release) at the frog neuromuscular junction. In the present study parallel experiments performed with these two toxins revealed that only glycerotoxin was able to release acetylcholine from Torpedo electric organ synaptosomes, while α-latrotoxin did not affect release in this system. In contrast, α-latrotoxin stimulated release of dopamine from PC12 cells (a cloned neurosecretory cell line), whereas glycerotoxin was almost inactive. In rat brain synaptosomes both toxins were active. Preincubation of synaptosomal membranes with glycerotoxin was without effect on the subsequent binding of α-latrotoxin. Glycerotoxin application induced depolarization of synaptosomal plasma membrane, massive Ca2+ influx, marked increase of the cytosolic Ca2+ concentration, and stimulation of catecholamine release. The latter effect occurred to the same extent when glycerotoxin was applied either in complete medium (containing both Ca2 and Mg2+), Ca2+ -free medium or divalent cation-free medium. Some of these effects of glycerotoxin in rat brain synaptosomes (depolarization, increased Ca2+ influx and increased cytosolic Ca2+ concentration) resemble effects previously reported for α-latrotoxin. However, the secretory response induced by the latter was reduced in Ca2+ -free, and abolished in divalent cation-free media. The different target specificity and the lack of binding competition of the two toxins could be due to their ability to recognize different receptors whose distribution overlap only in part in the cellular systems we have studied. The differences in action, on the other hand, could depend on postreceptor events, possibly related to the transmembrane insertion of toxin molecules demonstrated by others in artificial lipid membranes.

Original languageEnglish
Pages (from-to)939-949
Number of pages11
JournalNeuroscience
Volume12
Issue number3
DOIs
Publication statusPublished - 1984

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Neurotransmitter Agents
Synaptosomes
Divalent Cations
Acetylcholine
Electric Organ
Artificial Membranes
Torpedo
Neuromuscular Junction
PC12 Cells
Neurotoxins
Brain
glycerotoxin
Jaw
Anura
Catecholamines
Dopamine
Molecular Weight
Cell Membrane
Lipids
Cell Line

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

α-Latrotoxin and glycerotoxin differ in target specificity and in the mechanism of their neurotransmitter releasing action. / Madeddu, L.; Meldolesi, J.; Pozzan, T.; Sanclemente, L. E Cardona; Bon, C.

In: Neuroscience, Vol. 12, No. 3, 1984, p. 939-949.

Research output: Contribution to journalArticle

Madeddu, L. ; Meldolesi, J. ; Pozzan, T. ; Sanclemente, L. E Cardona ; Bon, C. / α-Latrotoxin and glycerotoxin differ in target specificity and in the mechanism of their neurotransmitter releasing action. In: Neuroscience. 1984 ; Vol. 12, No. 3. pp. 939-949.
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abstract = "α-Latrotoxin, a high molecular weight protein (130,000) purified from the venom of the black widow spider, and a partially purified neurotoxin, glycerotoxin, prepared from extracts of the jaw glands of the polichaete annelid Glycera convoluta, were previously found to induce similar effects (stimulation of quantal acetylcholine release) at the frog neuromuscular junction. In the present study parallel experiments performed with these two toxins revealed that only glycerotoxin was able to release acetylcholine from Torpedo electric organ synaptosomes, while α-latrotoxin did not affect release in this system. In contrast, α-latrotoxin stimulated release of dopamine from PC12 cells (a cloned neurosecretory cell line), whereas glycerotoxin was almost inactive. In rat brain synaptosomes both toxins were active. Preincubation of synaptosomal membranes with glycerotoxin was without effect on the subsequent binding of α-latrotoxin. Glycerotoxin application induced depolarization of synaptosomal plasma membrane, massive Ca2+ influx, marked increase of the cytosolic Ca2+ concentration, and stimulation of catecholamine release. The latter effect occurred to the same extent when glycerotoxin was applied either in complete medium (containing both Ca2 and Mg2+), Ca2+ -free medium or divalent cation-free medium. Some of these effects of glycerotoxin in rat brain synaptosomes (depolarization, increased Ca2+ influx and increased cytosolic Ca2+ concentration) resemble effects previously reported for α-latrotoxin. However, the secretory response induced by the latter was reduced in Ca2+ -free, and abolished in divalent cation-free media. The different target specificity and the lack of binding competition of the two toxins could be due to their ability to recognize different receptors whose distribution overlap only in part in the cellular systems we have studied. The differences in action, on the other hand, could depend on postreceptor events, possibly related to the transmembrane insertion of toxin molecules demonstrated by others in artificial lipid membranes.",
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