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

Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides

Bergmann, Timothy J. ; Fregno, Ilaria ; Fumagalli, Fiorenza ; Rinaldi, Andrea ; Bertoni, Francesco ; Boersema, Paul J. ; Picotti, Paola ; Molinari, Maurizio

In: Journal of biological chemistry, 2018, vol. 293, no. 15, p. 5600-5612

The stress sensors ATF6, IRE1, and PERK monitor deviations from homeostatic conditions in the endoplasmic reticulum (ER), a protein biogenesis compartment of eukaryotic cells. Their activation elicits unfolded protein responses (UPR) to reestablish proteostasis. UPR have been extensively investigated in cells exposed to chemicals that activate ER stress sensors by perturbing calcium, N-glycans,...