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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.

Mattiazzi M, Jambhekar A, Kaferle P, Derisi JL, Krizaj I, Petrovic U - Mol. Genet. Genomics (2010)

Bottom Line: We have conducted a genome-wide analysis of cellular effects of a PLA(2) in the yeast Saccharomyces cerevisiae as a model system.Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, 1000 Ljubljana, Slovenia.

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.

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Detailed representation of the interactions between the components of the gene network. The term “mixed interaction” is used to denote the presence of both types, congruent interactions and interactions whereby genes encoding the components of the complexes are both congruent and at the same time synthetically lethal, none of the types being predominant (see embedded tables for details). Numbers represent the raw values for synthetic lethality profile similarity (i.e., the number of genes in genetic interaction with both of the genes) and were obtained with the bioPixie tool (Myers et al. 2005, http://pixie.princeton.edu/pixie). (SYN-LETH synthetic lethality)
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Fig5: Detailed representation of the interactions between the components of the gene network. The term “mixed interaction” is used to denote the presence of both types, congruent interactions and interactions whereby genes encoding the components of the complexes are both congruent and at the same time synthetically lethal, none of the types being predominant (see embedded tables for details). Numbers represent the raw values for synthetic lethality profile similarity (i.e., the number of genes in genetic interaction with both of the genes) and were obtained with the bioPixie tool (Myers et al. 2005, http://pixie.princeton.edu/pixie). (SYN-LETH synthetic lethality)

Mentions: To define indirectly related genes and proteins with PLA2 genetic interactions, i.e., its process-specific network, we used the bioPIXIE bioinformatics tool (Myers et al. 2005) (Fig. 4). The RIM101 and RIM13 components of the Rim101 pathway are connected to this network primarily via interactions of RIM13, which has the highest confidence interactions with components of the prefoldin complex (GIM3/4/5 and YKE2). Indeed, gene set enrichment analysis of the network genes revealed the highest confidence level for three molecular complexes, SWR1 (P value 1.03e-10), retromer (P value 1.12e-6) and prefoldin (P value 3.35e-6), which, together with VPS1 and LGE1 genes, are central to the gene network thus obtained (Fig. 4). SWR1 complex is involved in chromatin remodeling, specifically it is required for the incorporation of the histone variant H2AZ into chromatin (Korber and Horz 2004). Retromer complex is an evolutionarily conserved protein complex involved in retrograde transport from endosomes to the Golgi apparatus (Verges 2008). Prefoldin complex is a heterohexameric cochaperone complex that delivers unfolded proteins, such as tubulin, to cytosolic chaperonin (Lopez-Fanarraga et al. 2001). These genes/complexes share many genetic interactions (Fig. 5), strongly indicating functional relations.Fig. 4


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.

Mattiazzi M, Jambhekar A, Kaferle P, Derisi JL, Krizaj I, Petrovic U - Mol. Genet. Genomics (2010)

Detailed representation of the interactions between the components of the gene network. The term “mixed interaction” is used to denote the presence of both types, congruent interactions and interactions whereby genes encoding the components of the complexes are both congruent and at the same time synthetically lethal, none of the types being predominant (see embedded tables for details). Numbers represent the raw values for synthetic lethality profile similarity (i.e., the number of genes in genetic interaction with both of the genes) and were obtained with the bioPixie tool (Myers et al. 2005, http://pixie.princeton.edu/pixie). (SYN-LETH synthetic lethality)
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Related In: Results  -  Collection

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Fig5: Detailed representation of the interactions between the components of the gene network. The term “mixed interaction” is used to denote the presence of both types, congruent interactions and interactions whereby genes encoding the components of the complexes are both congruent and at the same time synthetically lethal, none of the types being predominant (see embedded tables for details). Numbers represent the raw values for synthetic lethality profile similarity (i.e., the number of genes in genetic interaction with both of the genes) and were obtained with the bioPixie tool (Myers et al. 2005, http://pixie.princeton.edu/pixie). (SYN-LETH synthetic lethality)
Mentions: To define indirectly related genes and proteins with PLA2 genetic interactions, i.e., its process-specific network, we used the bioPIXIE bioinformatics tool (Myers et al. 2005) (Fig. 4). The RIM101 and RIM13 components of the Rim101 pathway are connected to this network primarily via interactions of RIM13, which has the highest confidence interactions with components of the prefoldin complex (GIM3/4/5 and YKE2). Indeed, gene set enrichment analysis of the network genes revealed the highest confidence level for three molecular complexes, SWR1 (P value 1.03e-10), retromer (P value 1.12e-6) and prefoldin (P value 3.35e-6), which, together with VPS1 and LGE1 genes, are central to the gene network thus obtained (Fig. 4). SWR1 complex is involved in chromatin remodeling, specifically it is required for the incorporation of the histone variant H2AZ into chromatin (Korber and Horz 2004). Retromer complex is an evolutionarily conserved protein complex involved in retrograde transport from endosomes to the Golgi apparatus (Verges 2008). Prefoldin complex is a heterohexameric cochaperone complex that delivers unfolded proteins, such as tubulin, to cytosolic chaperonin (Lopez-Fanarraga et al. 2001). These genes/complexes share many genetic interactions (Fig. 5), strongly indicating functional relations.Fig. 4

Bottom Line: We have conducted a genome-wide analysis of cellular effects of a PLA(2) in the yeast Saccharomyces cerevisiae as a model system.Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Biomedical Sciences, Jozef Stefan Institute, 1000 Ljubljana, Slovenia.

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.

Show MeSH