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

• Published in: Molecular genetics and genomics : MGG 2010-06, Vol.283 (6), p.519-530
• Main Authors: Mattiazzi, M, Jambhekar, A, Kaferle, P, DeRisi, J. L, Križaj, I, Petrovič, U
• Format: Article
• Language: English
• Subjects: Animal Genetics and Genomics; Biochemistry; Biomedical and Life Sciences; Cell cycle; Cell Membrane - chemistry; Cell Membrane - genetics; Cell Membrane - physiology; Cell Proliferation; Cell Shape - genetics; Endosomal membrane; Enzymes; Epistasis, Genetic - physiology; Fatty acids; Gene Regulatory Networks - physiology; Genetic interactions; Genetic Linkage; Genomes; Genomics; Human Genetics; Hydrogen-Ion Concentration; Hypotheses; Life Sciences; Membranes; Microbial Genetics and Genomics; Models, Biological; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Molecular Chaperones - physiology; Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Multiprotein Complexes - physiology; Neurotoxicity; Organisms, Genetically Modified; Original Paper; Phospholipase A; Phospholipases A2 - genetics; Physiology; Plant Genetics and Genomics; Proteins; Repressor Proteins - genetics; Rim101 pathway; Saccharomyces cerevisiae - cytology; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - growth & development; Saccharomyces cerevisiae - ultrastructure; Saccharomyces cerevisiae Proteins - genetics; Signal transduction; Signal Transduction - genetics; Signal Transduction - physiology; Yeast
• ISSN: 1617-4615; 1617-4623
• DOI: 10.1007/s00438-010-0533-8

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 A₂ (PLA₂s), 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 PLA₂ in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA₂ 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 PLA₂ 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.