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Université de Fribourg

Conserved functions of ether lipids and sphingolipids in the early secretory pathway

Jiménez-Rojo, Noemi ; Leonetti, Manuel D. ; Zoni, Valeria ; Colom, Adai ; Feng, Suihan ; Iyengar, Namrata R. ; Matile, Stefan ; Roux, Aurélien ; Vanni, Stefano ; Weissman, Jonathan S. ; Riezman, Howard

In: Current Biology, 2020, vol. 30, no. 19, p. 3775-3787.e7

Sphingolipids play important roles in physiology and cell biology, but a systematic examination of their functions is lacking. We performed a genome-wide CRISPRi screen in sphingolipid-depleted human cells and identified hypersensitive mutants in genes of membrane trafficking and lipid biosynthesis, including ether lipid synthesis. Systematic lipidomic analysis showed a coordinate regulation...

Université de Fribourg

From zero to six double bonds: phospholipid unsaturation and organelle function

Antonny, Bruno ; Vanni, Stefano ; Shindou, Hideo ; Thierry, Ferreira

In: Trends in Cell Biology, 2015, vol. 25, no. 7, p. 427–436

Cellular phospholipids (PLs) differ by the nature of their polar heads as well as by the length and unsaturation level of their fatty acyl chains. We discuss how the ratio between saturated, monounsaturated, and polyunsaturated PLs impacts on the functions of such organelles as the endoplasmic reticulum, synaptic vesicles, and photoreceptor discs. Recent experiments and simulations suggest...

Université de Fribourg

The yeast cell wall protein Pry3 inhibits mating through highly conserved residues within the CAP domain

Cottier, Stéphanie ; Darwiche, Rabih ; Meyenhofer, Felix ; Debelyy, Mykhaylo O. ; Schneiter, Roger

In: Biology Open, 2020, vol. 9, no. 6, p. bio053470

Members of the CAP/SCP/TAPS superfamily have been implicated in many different physiological processes, including pathogen defense, sperm maturation and fertilization. The mode of action of this class of proteins, however, remains poorly understood. The genome of Saccharomyces cerevisiae encodes three CAP superfamily members, Pry1-3. We have previously shown that Pry1 function is required...

Université de Fribourg

Proteomics-based monitoring of pathway activity reveals that blocking diacylglycerol biosynthesis rescues from alpha-synuclein toxicity

Soste, Martin ; Charmpi, Konstantina ; Lampert, Fabienne ; Gerez, Juan Atilio ; Oostrum, Marcvan ; Malinovska, Liliana ; Boersema, Paul Jonathan ; Prymaczok, Natalia Cecilia ; Riek, Roland ; Peter, Matthias ; Vanni, Stefano ; Beyer, Andreas ; Picotti, Paola

In: Cell Systems, 2019, vol. 9, no. 3, p. 309-320.e8

Proteinaceous inclusions containing alpha-synuclein (α-Syn) have been implicated in neuronal toxicity in Parkinson’s disease, but the pathways that modulate toxicity remain enigmatic. Here, we used a targeted proteomic assay to simultaneously measure 269 pathway activation markers and proteins deregulated by α-Syn expression across a panel of 33 Saccharomyces cerevisiae strains that...

Université de Fribourg

Ubiquitin release from eL40 is required for cytoplasmic maturation and function of 60S ribosomal subunits in Saccharomyces cerevisiae

Martín‐Villanueva, Sara ; Fernández‐Pevida, Antonio ; Fernández‐Fernández, José ; Kressler, Dieter ; Cruz, Jesús de la

In: The FEBS Journal, 2019, vol. 0, no. 0, p. -

Ubiquitin is generated by proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a linear polyubiquitin protein of head‐to‐tail monomers, or as a single N‐terminal moiety to one of two ribosomal proteins, eL40 (Ubi1/2 precursors) and eS31 (Ubi3 precursor). It has been proposed that the ubiquitin moiety fused to these ribosomal proteins could act...

Università della Svizzera italiana

Sumoylation regulates the stability and nuclease activity of Saccharomyces cerevisiae Dna2

Ranjha, Lepakshi ; Levikova, Maryna ; Altmannova, Veronika ; Krejci, Lumir ; Cejka, Petr

In: Communications Biology, 2019, vol. 2, p. 174

Dna2 is an essential nuclease-helicase that acts in several distinct DNA metabolic pathways including DNA replication and recombination. To balance these functions and prevent unscheduled DNA degradation, Dna2 activities must be regulated. Here we show that Saccharomyces cerevisiae Dna2 function is controlled by sumoylation. We map the sumoylation sites to the N-terminal regulatory domain of...

Université de Fribourg

Local accumulation of diacylglycerol alters membrane properties nonlinearly due to its transbilayer activity

Campomanes, Pablo ; Zoni, Valeria ; Vanni, Stefano

In: Communications Chemistry, 2019, vol. 2, no. 1, p. 72

Diacylglycerols (DAGs) are bioactive lipids that are ubiquitously present at low concentrations in cellular membranes. Upon the activation of lipid remodeling enzymes such as phospholipase C and phosphatidic acid phosphatase, DAG concentration increases, leading to a disruption of the lamellar phase of lipid membranes. To investigate the structural origin of these phenomena, here we develop ...

Université de Fribourg

Conventional and emerging roles of the energy sensor Snf1/AMPK in Saccharomyces cerevisiae

Coccetti, Paola ; Nicastro, Raffaele ; Tripodi, Farida

In: Microbial Cell, 2018, vol. 5, no. 11, p. 482–494

All proliferating cells need to match metabolism, growth and cell cycle progression with nutrient availability to guarantee cell viability in spite of a changing environment. In yeast, a signaling pathway centered on the effector kinase Snf1 is required to adapt to nutrient limitation and to utilize alternative carbon sources, such as sucrose and ethanol. Snf1 shares evolutionary conserved...