Raffaele Nicastro

Raffaele Nicastro
Université de Fribourg · Department Biology

PhD in Industrial Biotechnologies

About

19
Publications
12,814
Reads
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340
Citations
Additional affiliations
January 2017 - October 2021
Université de Fribourg
Position
  • PostDoc Position
January 2015 - December 2016
Università degli Studi di Milano-Bicocca
Position
  • PostDoc Position
January 2012 - December 2014
Università degli Studi di Milano-Bicocca
Position
  • PhD Student

Publications

Publications (19)
Article
Full-text available
The essential biometal manganese (Mn) serves as a cofactor for several enzymes that are crucial for the prevention of human diseases. Whether intracellular Mn levels may be sensed and modulate intracellular signaling events has so far remained largely unexplored. The highly conserved target of rapamycin complex 1 (TORC1, mTORC1 in mammals) protein...
Article
The endomembrane system of eukaryotic cells is essential for cellular homeostasis during growth and proliferation. Previous work showed that a central regulator of growth, namely the target of rapamycin complex 1 (TORC1), binds both membranes of vacuoles and signaling endosomes (SEs) that are distinct from multivesicular bodies (MVBs). Interestingl...
Preprint
The essential biometal manganese (Mn) functions as a cofactor for several enzymatic activities that are critical for the prevention of human diseases. Whether intracellular Mn levels may also modulate signaling events has so far remained largely unexplored. The target of rapamycin complex 1 (TORC1, mTORC1 in mammals) is a conserved protein kinase c...
Article
Full-text available
Indole-3-acetic acid (IAA) is the most common, naturally occurring phytohormone that regulates cell division, differentiation, and senescence in plants. The capacity to synthesize IAA is also widespread among plant-associated bacterial and fungal species, which may use IAA as an effector molecule to define their relationships with plants or to coor...
Article
Full-text available
Organelles of the endomembrane system maintain their identity and integrity during growth or stress conditions by homeostatic mechanisms that regulate membrane flux and biogenesis. At lysosomes and endosomes, the Fab1 lipid kinase complex and the nutrient-regulated target of rapamycin complex 1 (TORC1) control the integrity of the endolysosomal hom...
Article
Full-text available
All proliferating cells need to match metabolism, growth and cell cycle progression with nutrient availability to guarantee cell viability in spite of a changing environment. In yeast, a signaling pathway centered on the effector kinase Snf1 is required to adapt to nutrient limitation and to utilize alternative carbon sources, such as sucrose and e...
Article
Mitochondria play essential metabolic functions in eukaryotes. Although their major role is the generation of energy in the form of ATP, they are also involved in maintenance of cellular redox state, conversion and biosynthesis of metabolites and signal transduction. Most mitochondrial functions are conserved in eukaryotic systems and mitochondrial...
Article
Full-text available
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 es...
Article
Full-text available
Eukaryotic cell cycle progression through G 1 –S is driven by hormonal and growth-related signals that are transmitted by the target of rapamycin complex 1 (TORC1) pathway. In yeast, inactivation of TORC1 restricts G 1 –S transition due to the rapid clearance of G 1 cyclins (Cln) and the stabilization of the B-type cyclin (Clb) cyclin-dependent kin...
Article
Full-text available
We present an improved extraction and derivatization protocol for GCeMS analysis of amino/non-amino acids in Saccharomyces cerevisiae. Yeast cells were extracted with chloroform: aqueous-methanol (1:1, v/ v) and the resulting non-polar and polar extracts combined and dried for derivatization. Polar and non-polar metabolites were derivatized using t...
Article
Full-text available
In eukaryotes, nutrient availability and metabolism are coordinated by sensing mechanisms and signaling pathways, which influence a broad set of cellular functions such as transcription and metabolic pathways to match environmental conditions. In yeast, Protein Kinase A (PKA) is activated in the presence of high glucose concentrations, favoring fas...
Article
The metabolism of proliferating cells shows common features even in evolutionary distant organisms such as mammals and yeasts, for example the requirement for anabolic processes under tight control of signaling pathways. Analysis of the rewiring of metabolism, which occurs following the dysregulation of signaling pathways, provides new knowledge ab...
Article
Full-text available
Here we propose the optimization of a rapid and reproducible protocol for intracellular metabolite extraction from yeast cells and their metabolic profiling by 1H-NMR spectroscopy. The protocol reliability has been validated through the comparison between the metabolome of cells in different phases of growth or with different genetic backgrounds.
Article
Snf1, the yeast AMP-activated kinase homolog, regulates the expression of several genes involved in adaptation to glucose limitation and in response to cellular stresses. We previously demonstrated that Snf1 interacts with Swi6, the regulatory subunit of SBF and MBF complexes, and activates CLB5 transcription. Here we report that, in α-factor synch...
Article
Full-text available
In Saccharomyces cerevisiae, the entrance into S phase requires the activation of a specific burst of transcription, which depends on SBF (SCB binding factor, Swi4/Swi6) and MBF (MCB binding factor, Mbp1/Swi6) complexes. CK2 is a pleiotropic kinase involved in several cellular processes, including the regulation of the cell cycle. CK2 is composed o...

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Project (1)
Project
To address basic aspects of quiescence experimentally, we have chosen the unicellular eukaryote yeast Saccharomyces cerevisiae as a model system. Current data indicate that a conserved protein complex, coined target of rapamycin complex 1 (TORC1), plays a central role in yeast in coordinating both entry into and exit from G0 in response to nutrient levels. Interestingly, we discovered that amino acids represent essential and primordial signals that modulate TORC1 activity through the conserved Rag family GTPases. We are therefore currently addressing the molecular mechanism by which Rag GTPases sense amino acids and regulate TORC1 in yeast. Since some of the underlying mechanisms appear to be highly conserved, our studies may be helpful in understanding pathological conditions, including cancer, obesity, and type 2 diabetes, which are caused by deregulated TORC1 in humans.