Université de Fribourg

Spatially distinct pools of TORC1 balance protein homeostasis

Hatakeyama, Riko ; Péli-Gulli, Marie-Pierre ; Hu, Zehan ; Jaquenoud, Malika ; Osuna, Guillermo Miguel Garcia ; Sardu, Alessandro ; Dengjel, Jörn ; Virgilio, Claudio De

In: Molecular Cell, 2019, vol. 73, no. 2, p. 325-338.e8

The eukaryotic TORC1 kinase is a homeostatic controller of growth that integrates nutritional cues and mediates signals primarily from the surface of lysosomes or vacuoles. Amino acids activate TORC1 via the Rag GTPases that combine into structurally conserved multi-protein complexes such as the EGO complex (EGOC) in yeast. Here we show that Ego1, which mediates membrane-anchoring of EGOC via...

Université de Fribourg

The architecture of the Rag GTPase signaling network

Nicastro, Raffaele ; Sardu, Alessandro ; Panchaud, Nicolas ; De Virgilio, Claudio

In: Biomolecules, 2017, vol. 7, no. 3, p. 48

The evolutionarily conserved target of rapamycin complex 1 (TORC1) couples an array of intra- and extracellular stimuli to cell growth, proliferation and metabolism, and its deregulation is associated with various human pathologies such as immunodeficiency, epilepsy, and cancer. Among the diverse stimuli impinging on TORC1, amino acids represent essential input signals, but how they control...

Université de Fribourg

Amino Acids Stimulate TORC1 through Lst4-Lst7, a GTPase-Activating Protein Complex for the Rag Family GTPase Gtr2

Péli-Gulli, Marie-Pierre ; Sardu, Alessandro ; Panchaud, Nicolas ; Raucci, Serena ; Virgilio, Claudio De

In: Cell Reports, 2015, vol. 13, no. 1, p. 1–7

Rag GTPases assemble into heterodimeric complexes consisting of RagA or RagB and RagC or RagD in higher eukaryotes, or Gtr1 and Gtr2 in yeast, to relay amino acid signals toward the growth-regulating target of rapamycin complex 1 (TORC1). The TORC1-stimulating state of Rag GTPase heterodimers, containing GTP- and GDP-loaded RagA/B/Gtr1 and RagC/D/Gtr2, respectively, is maintained in part by the...

Université de Fribourg

The I-BAR protein Ivy1 is an effector of the Rab7 GTPase Ypt7 involved in vacuole membrane homeostasis

Numrich, Johannes ; Péli-Gulli, Marie-Pierre ; Arlt, Henning ; Sardu, Alessandro ; Griffith, Janice ; Levine, Tim ; Engelbrecht-Vandré, Siegfried ; Reggiori, Fulvio ; De Virgilio, Claudio ; Ungermann, Christian

In: Journal of Cell Science, 2015, vol. 128, no. 13, p. 2278–2292

Membrane fusion at the vacuole depends on a conserved machinery that includes SNAREs, the Rab7 homolog Ypt7 and its effector HOPS. Here, we demonstrate that Ypt7 has an unexpected additional function by controlling membrane homeostasis and nutrient-dependent signaling on the vacuole surface. We show that Ivy1, the yeast homolog of mammalian missing-in-metastasis (MIM), is a vacuolar effector of...

Université de Fribourg

Transcriptome structure variability in Saccharomyces cerevisiae strains determined with a newly developed assembly software

Sardu, Alessandro ; Treu, Laura ; Campanaro, Stefano

In: BMC Genomics, 2014, vol. 15, no. 1, p. 1045

RNA-seq studies have an important role for both large-scale analysis of gene expression and for transcriptome reconstruction. However, the lack of software specifically developed for the analysis of the transcriptome structure in lower eukaryotes, has so far limited the comparative studies among different species and strains.Results: In order to fill this gap, an innovative software called ORA...