A neurotoxic phospholipase A2 impairs yeast amphiphysin activity and reduces endocytosis

Abstract

Background: Presynaptically neurotoxic phospholipases A2 inhibit synaptic vesicle recycling through endocytosis. Principal Findings: Here we provide insight into the action of a presynaptically neurotoxic phospholipase A2 ammodytoxin A (AtxA) on clathrin-dependent endocytosis in budding yeast. AtxA caused changes in the dynamics of vesicle formation and scission from the plasma membrane in a phospholipase activity dependent manner. Our data, based on synthetic dosage lethality screen and the analysis of the dynamics of sites of endocytosis, indicate that AtxA impairs the activity of amphiphysin. Conclusions: We identified amphiphysin and endocytosis as the target of AtxA intracellular activity. We propose that AtxA reduces endocytosis following a mechanism of action which includes both a specific protein-protein interaction and enzymatic activity, and which is applicable to yeast and mammalian cells. Knowing how neurotoxic phospholipases A2 work can open new ways to regulate endocytosis. © 2012 Mattiazzi et al.