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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

Lipid droplet biogenesis from specialized ER subdomains

Choudhary, Vineet ; Schneiter, Roger

In: Microbial Cell, 2020, vol. 7, no. 8, p. 218–221

Lipid droplets (LDs) are cellular compartments dedicated to the storage of metabolic energy in the form of neutral lipids, commonly known as “fat”. The biogenesis of LDs takes place in the endoplasmic reticulum (ER), but its spatial and temporal organization is poorly understood. How exactly sites of LD formation are selected and the succession of proteins and lipids needed to mediate...

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

Structure and dynamics of the acyl chains in the membrane trafficking and enzymatic processing of lipids

Vanni, Stefano ; Riccardi, Laura ; Palermo, Giulia ; De Vivo, Marco

In: Accounts of Chemical Research, 2019, vol. 52, no. 11, p. 3087–3096

The regulatory chemical mechanisms of lipid trafficking and degradation are involved in many pathophysiological processes, being implicated in severe pain, inflammation, and cancer. In addition, the processing of lipids is also relevant for industrial and environmental applications. However, there is poor understanding of the chemical features that control lipid membrane trafficking and allow...

Università della Svizzera italiana

Quality control mechanisms of protein biogenesis : proteostasis dies hard

Bergmann, Timothy Jan ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: AIMS biophysics, 2016, vol. 3, no. 4, p. 456-478

The biosynthesis of proteins entails a complex series of chemical reactions that transform the information stored in the nucleic acid sequence into a polypeptide chain that needs to properly fold and reach its functional location in or outside the cell. It is of no surprise that errors might occur that alter the polypeptide sequence leading to a non-functional proteins or that impede delivery...

Université de Fribourg

A spatially and functionally distinct pool of TORC1 defines signaling endosomes in yeast

Hatakeyama, Riko ; De Virgilio, Claudio

In: Autophagy, 2019, vol. 15, no. 5, p. 915–916

The evolutionarily conserved target of rapamycin complex 1 (TORC1) regulates cell growth in a homeostatic manner by tuning anabolic and catabolic processes in response to nutritional and hormonal cues. Interestingly, rather than being localized at the plasma membrane as perhaps expected for an integrator of extracellular signals, TORC1 mainly localizes at vacuolar (in yeast) and lysosomal (in...

Université de Fribourg

Spatially distinct pools of TORC1 balance protein homeostasis

Hatakeyama, Riko ; Péli-Gulli, Marie-Pierre ; Hu, Zehan ; Jaquenoud, Malika ; Osuna, Guillermo Miguel Garcia ; Sardu, Alessandro ; Dengjel, Jörn ; Virgilio, Claudio De

In: Molecular Cell, 2019, vol. 73, no. 2, p. 325-338.e8

The eukaryotic TORC1 kinase is a homeostatic controller of growth that integrates nutritional cues and mediates signals primarily from the surface of lysosomes or vacuoles. Amino acids activate TORC1 via the Rag GTPases that combine into structurally conserved multi-protein complexes such as the EGO complex (EGOC) in yeast. Here we show that Ego1, which mediates membrane-anchoring of EGOC via...

Université de Fribourg

The impact of ESCRT on Aβ1-42 induced membrane lesions in a yeast model for Alzheimer’s disease

Fruhmann, Gernot ; Marchal, Christelle ; Vignaud, Hélène ; Verduyckt, Mathias ; Talarek, Nicolas ; De Virgilio, Claudio ; Winderickx, Joris ; Cullin, Christophe

In: Frontiers in Molecular Neuroscience, 2018, vol. 11, p. -

Aβ metabolism plays a pivotal role in Alzheimer’s disease. Here, we used a yeast model to monitor Aβ42 toxicity when entering the secretory pathway and demonstrate that processing in, and exit from the endoplasmic reticulum (ER) is required to unleash the full Aβ42 toxic potential. Consistent with previously reported data, our data suggests that Aβ42 interacts with mitochondria, thereby...

Université de Fribourg

Seeing is better than believing: visualization of membrane transport in plants

Geisler, Markus

In: Current Opinion in Plant Biology, 2018, vol. 46, p. 104–112

Recently, the plant transport field has shifted their research focus toward a more integrative investigation of transport networks thought to provide the basis for long- range transport routes. Substantial progress was provided by of a series of elegant techniques that allow for a visualization or prediction of substrate movements in plant tissues in contrast to established quantitative...