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

The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability

Wilms, Tobias ; Swinnen, Erwin ; Eskes, Elja ; Dolz-Edo, Laura ; Uwineza, Alice ; Essche, Ruben Van ; Rosseels, Joëlle ; Zabrocki, Piotr ; Cameroni, Elisabetta ; Franssens, Vanessa ; Virgilio, Claudio De ; Smits, Gertien J. ; Winderickx, Joris

In: PLOS Genetics, 2017, vol. 13, no. 6, p. e1006835

The evolutionary conserved TOR complex 1 controls growth in response to the quality and quantity of nutrients such as carbon and amino acids. The protein kinase Sch9 is the main TORC1 effector in yeast. However, only few of its direct targets are known. In this study, we performed a genome-wide screening looking for mutants which require Sch9 function for their survival and growth. In this...

Université de Fribourg

Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V-ATPase

Dechant, Reinhard ; Binda, Matteo ; Lee, Sung Sik ; Pelet, Serge ; Winderickx, Joris ; Peter, Matthias

In: Embo Journal, 2010, vol. 29, no. 15, p. 2515-2526

Glucose is the preferred carbon source for most cell types and a major determinant of cell growth. In yeast and certain mammalian cells, glucose activates the cAMP-dependent protein kinase A (PKA), but the mechanisms of PKA activation remain unknown. Here, we identify cytosolic pH as a second messenger for glucose that mediates activation of the PKA pathway in yeast. We find that cytosolic pH is...

Université de Fribourg

Life in the midst of scarcity: adaptations to nutrient availability in Saccharomyces cerevisiae

Smets, Bart ; Ghillebert, Ruben ; Snijder, Pepijn De ; Binda, Matteo ; Swinnen, Erwin ; De Virgilio, Claudio ; Winderickx, Joris

In: Current Genetics, 2010, vol. 56, no. 1, p. 1-32

Cells of all living organisms contain complex signal transduction networks to ensure that a wide range of physiological properties are properly adapted to the environmental conditions. The fundamental concepts and individual building blocks of these signalling networks are generally well-conserved from yeast to man; yet, the central role that growth factors and hormones play in the regulation of...

Université de Fribourg

Phosphorylation, lipid raft interaction and traffic of α-synuclein in a yeast model for Parkinson

Zabrocki, Piotr ; Bastiaens, Ilse ; Delay, Charlotte ; Bammens, Tine ; Ghillebert, Ruben ; Pellens, Klaartje ; Virgilio, Claudio De ; Leuven, Fred Van ; Winderickx, Joris

In: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, 2008, vol. 1783, no. 10, p. 1767-1780

Parkinson's disease is a neurodegenerative disorder characterized by the formation of Lewy bodies containing aggregated α-synuclein. We used a yeast model to screen for deletion mutants with mislocalization and enhanced inclusion formation of α-synuclein. Many of the mutants were affected in functions related to vesicular traffic but especially mutants in endocytosis and vacuolar degradation...