Neurotoxic phospholipase A2 toxicity model: an insight from mammalian cells

Nina Vardjan, Mojca Mattiazzi, Edward G. Rowan, Igor Križaj, Uros̀ Petrovič, Toni Petan

Research output: Contribution to journalArticle

5 Citations (Scopus)
9 Downloads (Pure)

Abstract

The molecular mechanism of action of presynaptically neurotoxic secreted phospholipases A2 (sPLA2s) has not been fully elucidated. We have recently proposed a model to explain one of the hallmarks of their action - the reduction in endocytosis leading to synaptic vesicle depletion in nerve terminals. Our results speak strongly in favor of a mechanism in which both specific protein-protein interactions and enzymatic activity of the neurotoxic sPLA2 ammodytoxin A (AtxA) are necessary for impairment of clathrin-dependent endocytosis in yeast cells. The reduction of endocytosis was strictly dependent on the enzymatic activity of sPLA2s expressed ectopically in our yeast model cells and was not observedwith the catalytically inactive, non-neurotoxic AtxA-homolog, ammodytin L (AtnL). Here weconfirm the validity of the model in mammalian cells also, by demonstrating that the enzymatically active mutant of AtnL, shown to inhibit endocytosis in yeast, acts as a presynaptically neurotoxic sPLA2 at the mammalian neuromuscular junction.

Original languageEnglish
Article numbere23600
Number of pages3
JournalCommunicative and Integrative Biology
Volume6
Issue number3
DOIs
Publication statusPublished - 9 Apr 2013

Keywords

  • ammodytin
  • ammodytoxin
  • endocytosis
  • myotoxicity
  • neuromuscular activity
  • presynaptic neurotoxicity
  • secreted phospholipase A

Cite this