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.
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.
Mattiazzi
M
M
Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, 1000 Ljubljana, Slovenia.
Jambhekar
A
A
Kaferle
P
P
Derisi
J L
JL
Krizaj
I
I
Petrovic
U
U
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
D018832:Molecular Chaperones; D046912:Multiprotein Complexes; C489601:RIM101 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; C112806:prefoldin; D054467:Phospholipases A2