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Université de Fribourg

Orm1 and Orm2 are conserved endoplasmic reticulum membrane proteins regulating lipid homeostasis and protein quality control

Han, Sumin ; Lone, Museer A. ; Schneiter, Roger ; Chang, Amy

In: Proceedings of the National Academy of Sciences - PNAS, 2010, p. -

Yeast members of the ORMDL family of endoplasmic reticulum (ER) membrane proteins play a central role in lipid homeostasis and protein quality control. In the absence of yeast Orm1 and Orm2, accumulation of long chain base, a sphingolipid precursor, suggests dysregulation of sphingolipid synthesis. Physical interaction between Orm1 and Orm2 and serine palmitoyltransferase, responsible for the...

Université de Fribourg

Integral membrane proteins Brr6 and Apq12 link assembly of the nuclear pore complex to lipid homeostasis in the endoplasmic reticulum

Hodge, Christine A. ; Choudhary, Vineet ; Wolyniak, Michael J. ; Scarcelli, John J. ; Schneiter, Roger ; Cole, Charles N.

In: Journal of Cell Science, 2010, vol. 123, p. 141-151

Cells of Saccharomyces cerevisiae lacking Apq12, a nuclear envelope (NE)-endoplasmic reticulum (ER) integral membrane protein, are defective in assembly of nuclear pore complexes (NPCs), possibly because of defects in regulating membrane fluidity. We identified BRR6, which encodes an essential integral membrane protein of the NE-ER, as a dosage suppressor of apq12δ. Cells...

Université de Fribourg

Monitoring sterol uptake, acetylation, and export in yeast

Choudhary, Vineet ; Schneiter, Roger

In: Methods in Molecular Biology, 2009, vol. 580, p. 221-232

Sterols are essential lipid components of eukaryotic membranes. They are synthesized in the endoplasmatic reticulum (ER) from where they are efficiently transported to the plasma membrane, which harbors ~90% of the free sterol pool of the cell. The molecular mechanisms that govern this lipid transport, however, are not well characterized and are challenging to analyze. Saccharomyces cerevisiae...

Université de Fribourg

Membrane rafts are involved in intracellular miconazole accumulation in yeast cells

François, Isabelle E. J. A. ; Bink, Anna ; Vandercappellen, Jo ; Ayscough, Kathryn R. ; Toulmay, Alexandre ; Schneiter, Roger ; Gyseghem, Elke van ; Mooter, Guy Van den ; Borgers, Marcel ; Vandenbosch, Davy ; Coenye, Tom ; Cammue, Bruno P. A. ; Thevissen, Karin

In: The Journal of Biological Chemistry, 2009, vol. 284, p. 32680-32685

Azoles inhibit ergosterol biosynthesis, resulting in ergosterol depletion and accumulation of toxic 14α-methylated sterols in membranes of susceptible yeast. We demonstrated previously that miconazole induces actin cytoskeleton stabilization in Saccharomyces cerevisiae prior to induction of reactive oxygen species, pointing to an ancillary mode of action. Using a genome-wide agar-based...

Université de Fribourg

The Cdc42 effectors ste20, Cla4, and Skm1 down-regulate the expression of genes involved in sterol uptake by a mitogen-activated protein kinase-independent pathway

Lin, Meng ; Unden, Heike ; Jacquier, Nicolas ; Schneiter, Roger ; Just, Ursula ; Höfken, Thomas

In: Molecular Biology of the Cell, 2009, vol. 20, no. 22, p. 4826-4837

In Saccharomyces cerevisiae, the Rho-type GTPase Cdc42 regulates polarized growth through its effectors, including the p21-activated kinases (PAKs) Ste20, Cla4, and Skm1. Previously, we demonstrated that Ste20 interacts with several proteins involved in sterol synthesis that are crucial for cell polarization. Under anaerobic conditions, sterols cannot be synthesized and need to be imported into...

Université de Fribourg

Mitochondrial outer membrane proteins assist Bid in Bax-mediated lipidic pore formation

Schafer, Blanca ; Quispe, Joel ; Choudhary, Vineet ; Chipuk, Jerry E. ; Ajero, Teddy G. ; Du, Han ; Schneiter, Roger ; Kuwana, Tomomi

In: Molecular Biology of The Cell, 2009, vol. 20, no. 8, p. 2276-2285

Mitochondrial outer membrane permeabilization (MOMP) is a critical step in apoptosis and is regulated by Bcl-2 family proteins. In vitro systems using cardiolipin-containing liposomes have demonstrated the key features of MOMP induced by Bax and cleaved Bid; however, the nature of the "pores" and how they are formed remain obscure. We found that mitochondrial outer membranes contained very little...

Université de Fribourg

An acetylation/deacetylation cycle controls the export of sterols and steroids from S. cerevisiae

Tiwari, Rashi ; Köffel, René ; Schneiter, Roger

In: The EMBO Journal, 2007, vol. 26, no. 24, p. 5109–5119

Sterol homeostasis in eukaryotic cells relies on the reciprocal interconversion of free sterols and steryl esters. Here we report the identification of a novel reversible sterol modification in yeast, the sterol acetylation/deacetylation cycle. Sterol acetylation requires the acetyltransferase ATF2, whereas deacetylation requires SAY1, a membrane-anchored deacetylase with a putative active site...

Université de Fribourg

Lipid signalling in disease

Wymann, Matthias P. ; Schneiter, Roger

In: Nature Reviews Molecular Cell Biology, 2008, vol. 9, p. 162-176

Université de Fribourg

The role of lipids in the biogenesis of integral membrane proteins

Schneiter, Roger ; Toulmay, Alexandre

In: Applied Microbiology and Biotechnology, 2007, vol. 73, no. 6, p. 1224-1232

Most integral membrane proteins are cotranslationally inserted into the lipid bilayer. In prokaryotes, membrane insertion of the nascent chain takes place at the plasma membrane, whereas in eukaryotes insertion takes place into the endoplasmatic reticulum. In both kingdoms of life, however, the same membrane that acquaints the newly born membrane protein also synthesizes the bilayer lipids...

Université de Fribourg

Lipid-dependent surface transport of the proton pumping ATPase: A model to study plasma membrane biogenesis in yeast

Toulmay, Alexandre ; Schneiter, Roger

In: Biochimie, 2007, vol. 89, no. 2, p. 249-254

The proton pumping H+-ATPase, Pma1, is one of the most abundant integral membrane proteins of the yeast plasma membrane. Pma1 activity controls the intracellular pH and maintains the electrochemical gradient across the plasma membrane, two essential cellular functions. The maintenance of the proton gradient, on the other hand, also requires a specialized lipid composition of this membrane. The...