Université de Fribourg

TORC1 specifically inhibits microautophagy through ESCRT-0

Hatakeyama, Riko ; Virgilio, Claudio De

In: Current Genetics, 2019, vol. 65, no. 5, p. 1243–1249

Nutrient starvation induces the degradation of specific plasma membrane proteins through the multivesicular body (MVB) sorting pathway and of vacuolar membrane proteins through microautophagy. Both of these processes require the gateway protein Vps27, which recognizes ubiquitinated cargo proteins at phosphatidylinositol 3-phosphate-rich membranes as part of a heterodimeric complex coined...

Université de Fribourg

Multilayered control of protein turnover by torc1 and atg1

Hu, Zehan ; Raucci, Serena ; Jaquenoud, Malika ; Hatakeyama, Riko ; Stumpe, Michael ; Rohr, Rudolf ; Reggiori, Fulvio ; Virgilio, Claudio De ; Dengjel, Jörn

In: Cell Reports, 2019, vol. 28, no. 13, p. 3486-3496.e6

The target of rapamycin complex 1 (TORC1) is a master regulator of cell homeostasis, which promotes anabolic reactions and synchronously inhibits catabolic processes such as autophagy-mediated protein degradation. Its prime autophagy target is Atg13, a subunit of the Atg1 kinase complex that acts as the gatekeeper of canonical autophagy. To study whether the activities of TORC1 and Atg1 are...

Université de Fribourg

A spatially and functionally distinct pool of TORC1 defines signaling endosomes in yeast

Hatakeyama, Riko ; De Virgilio, Claudio

In: Autophagy, 2019, vol. 15, no. 5, p. 915–916

The evolutionarily conserved target of rapamycin complex 1 (TORC1) regulates cell growth in a homeostatic manner by tuning anabolic and catabolic processes in response to nutritional and hormonal cues. Interestingly, rather than being localized at the plasma membrane as perhaps expected for an integrator of extracellular signals, TORC1 mainly localizes at vacuolar (in yeast) and lysosomal (in...

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

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

Ypk1/Ypk2 kinases maintain Rho1 at the plasma membrane by flippase-dependent lipid remodelling after membrane stresses

Hatakeyama, Riko ; Kono, Keiko ; Yoshida, Satoshi

In: J Cell Sci, 2017, p. jcs.198382

The plasma membrane (PM) is frequently challenged by mechanical stresses. In budding yeast, TORC2-Ypk1/Ypk2 kinase cascade plays a critical role in PM stress responses by reorganizing the actin cytoskeleton via Rho1 GTPase. However, the molecular mechanism by which TORC2-Ypk1/Ypk2 regulates Rho1 is not well defined. Here, we found that Ypk1/Ypk2 maintain PM localization of Rho1 under PM...