Université de Fribourg

Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure

Zoni, Valeria ; Khaddaj, Rasha ; Lukmantara, Ivan ; Shinoda, Wataru ; Hongyuan, Yang ; Schneiter, Roger ; Vanni, Stefano

In: Proceedings of the National Academy of Sciences, 2021, vol. 118, no. 10, p. e2017205118

Lipid droplets (LDs) are intracellular organelles responsible for lipid storage, and they emerge from the endoplasmic reticulum (ER) upon the accumulation of neutral lipids, mostly triglycerides (TG), between the two leaflets of the ER membrane. LD biogenesis takes place at ER sites that are marked by the protein seipin, which subsequently recruits additional proteins to catalyze LD formation....

Université de Fribourg

Estimating the accuracy of the MARTINI model towards the investigation of Peripheral Protein-Membrane Interactions

Srinivasan, Sriraksha ; Zoni, Valeria ; Vanni, Stefano

In: Faraday Discussions, 2020, p. -

Peripheral membrane proteins play a major role in numerous biological processes by transiently associating with cellular membranes, often with extreme membrane specificity. Because of the short-lived nature of these interactions, molecular dynamics (MD) simulations have emerged as an appealing tool to characterize at the structural level the molecular details of the protein-membrane...

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

Accurate estimation of membrane capacitance from atomistic molecular dynamics simulations of zwitterionic lipid bilayers

Ardham, Vikram Reddy ; Zoni, Valeria ; Adamowicz, Sylvain ; Campomanes, Pablo ; Vanni, Stefano

In: The Journal of Physical Chemistry B, 2020, vol. 124, no. 38, p. 8278–8286

Lipid membranes are indispensable to life, and they regulate countless cellular processes. To investigate the properties of membranes under controlled conditions, numerous reconstitution methods have been developed over the last few decades. Several of these methods result in the formation of lipid bilayers containing residual hydrophobic molecules between the two monolayers. These...

Université de Fribourg

Phosphatidylserine transport by ORP/Osh proteins is driven by phosphatidylinositol 4-phosphate

Filseck, Joachim Moser von ; Čopič, Alenka ; Delfosse, Vanessa ; Vanni, Stefano ; Jackson, Catherine L. ; Bourguet, William ; Drin, Guillaume

In: Science, 2015, vol. 349, no. 6246, p. 432–436

In eukaryotic cells, phosphatidylserine (PS) is synthesized in the endoplasmic reticulum (ER) but is highly enriched in the plasma membrane (PM), where it contributes negative charge and to specific recruitment of signaling proteins. This distribution relies on transport mechanisms whose nature remains elusive. Here, we found that the PS transporter Osh6p extracted phosphatidylinositol...

Université de Fribourg

Methyl-branched lipids promote the membrane adsorption of α-synuclein by enhancing shallow lipid-packing defects

Garten, Matthias ; Prévost, Coline ; Cadart, Clotilde ; Gautier, Romain ; Bousset, Luc ; Melki, Ronald ; Bassereau, Patricia ; Vanni, Stefano

In: Physical Chemistry Chemical Physics, 2015, vol. 17, no. 24, p. 15589–15597

Alpha-synuclein (AS) is a synaptic protein that is directly involved in Parkinson's disease due to its tendency to form protein aggregates. Since AS aggregation can be dependent on the interactions between the protein and the cell plasma membrane, elucidating the membrane binding properties of AS is of crucial importance to establish the molecular basis of AS aggregation into toxic fibrils....

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

How do ethanolamine plasmalogens contribute to order and structure of neurological membranes?

West, Ana ; Zoni, Valeria ; Teague, Walter E. ; Leonard, Alison N. ; Vanni, Stefano ; Gawrisch, Klaus ; Tristram-Nagle, Stephanie ; Sachs, Jonathan N. ; Klauda, Jeffery B.

In: The Journal of Physical Chemistry B, 2020, vol. 124, no. 5, p. 828–839

Ethanolamine plasmalogen (EtnPLA) is a conical-shaped ether lipid and an essential component of neurological membranes. Low stability against oxidation limits its study in experiments. The concentration of EtnPLA in the bilayer varies depending on cell type and disease progression. Here we report on mixed bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-(1Z-...

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...

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...