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...

Università della Svizzera italiana

Regulatory control of DNA end resection by Sae2 phosphorylation

Cannavo, Elda ; Johnson, Dominic ; Andres, Sara N. ; Kissling, Vera M. ; Reinert, Julia K. ; Garcia, Valerie ; Erie, Dorothy A. ; Hess, Daniel ; Thomä, Nicolas H. ; Enchev, Radoslav I. ; Peter, Matthias ; Williams, R. Scott ; Neale, Matt J. ; Cejka, Petr

In: Nature communications, 2018, vol. 9, p. 4016

DNA end resection plays a critical function in DNA double-strand break repair pathway choice. Resected DNA ends are refractory to end-joining mechanisms and are instead channeled to homology-directed repair. Using biochemical, genetic, and imaging methods, we show that phosphorylation of Saccharomyces cerevisiae Sae2 controls its capacity to promote the Mre11-Rad50-Xrs2 (MRX) nuclease to...

Université de Fribourg

Functional mapping of yeast genomes by saturated transposition

Michel, Agnès Henria ; Hatakeyama, Riko ; Kimmig, Philipp ; Arter, Meret ; Peter, Matthias ; Matos, Joao ; Virgilio, Claudio De ; Kornmann, Benoît

In: eLife, 2017, vol. 6, p. e23570

Yeast is a powerful model for systems genetics. We present a versatile, time- and labor-efficient method to functionally explore the Saccharomyces cerevisiae genome using saturated transposon mutagenesis coupled to high-throughput sequencing. SAturated Transposon Analysis in Yeast (SATAY) allows one-step mapping of all genetic loci in which transposons can insert without disrupting essential...

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...