title: A neurotoxic phospholipase A2 impairs yeast amphiphysin activity and reduces endocytosis.
abstract: BACKGROUND
  Presynaptically neurotoxic phospholipases A(2) inhibit synaptic vesicle recycling through endocytosis.
  
  
  RESULTS
  Here we provide insight into the action of a presynaptically neurotoxic phospholipase A(2) 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 A(2) work can open new ways to regulate endocytosis.
authors: Department of Molecular and Biomedical Sciences, Jožef Stefan Institute, Ljubljana, Slovenia.
authors: Mojca
authors: M
authors: Mattiazzi
authors: Yidi
authors: Y
authors: Sun
authors: Heimo
authors: H
authors: Wolinski
authors: Andrej
authors: A
authors: Bavdek
authors: Toni
authors: T
authors: Petan
authors: Gregor
authors: G
authors: Anderluh
authors: Sepp D
authors: SD
authors: Kohlwein
authors: David G
authors: DG
authors: Drubin
authors: Igor
authors: I
authors: Križaj
authors: Uroš
authors: U
authors: Petrovič
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors*; D004705:Endocytosis / Q000187:drug effects* / Q000235:genetics; D023281:Genomics; D008840:Microfilament Proteins / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D009498:Neurotoxins / Q000633:toxicity*; D054467:Phospholipases A2 / Q000633:toxicity*; D010743:Phospholipids / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; C075852:BMH1 protein, S cerevisiae; C097164:BMH2 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D010743:Phospholipids; C089181:RVS161 protein, S cerevisiae; C082282:RVS167 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C075637:amphiphysin; D054467:Phospholipases A2