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A mammalian phospholipase A 2 in yeast: a global view
Author(s) -
Mattiazzi M.,
Petroviè U.,
DeRisi J.L.,
Križaj I.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a952
Subject(s) - biology , saccharomyces cerevisiae , yeast , microbiology and biotechnology , gene , genetics
Secretory phospholipases A 2 (sPLA 2 s) are mammalian enzymes involved in a wide range of (patho)physiological processes such as inflammation, apoptosis, tumour resistance and neurotoxicity. Our laboratory has been using yeast Saccharomyces cerevisiae as a model to study the molecular mechanism of the cellular effects of sPLA 2 s, with ammodytoxin (Atx), a sPLA 2 from the venom of the long‐nosed viper, as a representative molecule. Intracellular binding proteins of Atx include 14‐3‐3 proteins and calmodulin, both evolutionarily highly conserved regulatory proteins present in all eukaryotic cells. Because of its several molecular targets, Atx is a multifunctional protein, consequently to assess the molecular mechanisms of its effects global approaches such as gene expression analysis, using whole‐genome DNA microarrays, and mutant phenotypic analysis, using the collection of all single gene knock‐out yeast strains, have been used in addition to classic techniques. Intracellular activity in yeast was determined and a number of phenotypes caused by Atx expression, such as inhibition of G 2 cell cycle arrest, peroxisome proliferation, induction of mating projections formation, pseudohyphal growth, fragmentation of cortical actin patches and increase of bulk exocytosis, were observed. Besides deciphering the mechanism of sPLA 2 s action, this work represents the first step towards a novel screening strategy for identification of deacylating phospholipases encoding yeast genes. The work has been supported by the Slovenian Research Agency grant J1‐6507.