title: Genetic interactions between a phospholipase A2 and the Rim101 pathway components in S. cerevisiae reveal a role for this pathway in response to changes in membrane composition and shape.
abstract: Modulating composition and shape of biological membranes is an emerging mode of regulation of cellular processes. We investigated the global effects that such perturbations have on a model eukaryotic cell. Phospholipases A(2) (PLA(2)s), enzymes that cleave one fatty acid molecule from membrane phospholipids, exert their biological activities through affecting both membrane composition and shape. We have conducted a genome-wide analysis of cellular effects of a PLA(2) in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA(2) activity and the Rim101 signaling pathway in S. cerevisiae. Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway. We describe a genetically and functionally related network, consisting of components of the Rim101 pathway and the prefoldin, retromer and SWR1 complexes, and predict its functional relation to PLA(2) activity in a model eukaryotic cell. This study provides a list of the players involved in the global response to changes in membrane composition and shape in a model eukaryotic cell, and further studies are needed to understand the precise molecular mechanisms connecting them.
authors.affiliation: Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, 1000 Ljubljana, Slovenia.
authors.forename: M
authors.initials: M
authors.lastname: Mattiazzi
authors.forename: A
authors.initials: A
authors.lastname: Jambhekar
authors.forename: P
authors.initials: P
authors.lastname: Kaferle
authors.forename: J L
authors.initials: JL
authors.lastname: Derisi
authors.forename: I
authors.initials: I
authors.lastname: Krizaj
authors.forename: U
authors.initials: U
authors.lastname: Petrovic
mesh_terms: D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D048430:Cell Shape / Q000235:genetics*; D004843:Epistasis, Genetic / Q000502:physiology; D053263:Gene Regulatory Networks / Q000502:physiology; D008040:Genetic Linkage; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D030781:Organisms, Genetically Modified; D054467:Phospholipases A2 / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C489601:RIM101 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C112806:prefoldin; D054467:Phospholipases A2