Cell growth control by nutrients: focus on mTOR and class III PI3K
Event details
| Date | 06.03.2017 |
| Hour | 13:30 › 14:30 |
| Speaker | Mario PENDE Institut Necker, Paris, France |
| Location | |
| Category | Conferences - Seminars |
SEMINAR SERIES : Trends in Physiology and Metabolism (Bio-682)
Abstract:
In metazoans, nutrient and growth factor availability control cell number, size and metabolic homeostasis. We investigate the specific programs underlying these responses, and their coordination by signal transduction mechanisms.We focus on two nutrient signal transduction pathways, the mTOR (mammalian Target Of Rapamycin) and the Vps15/Vps34 complex (Vacuolar Protein Sorting15/34). These ancient pathways are present in every eukaryotic cell, from unicellular organisms like yeast to humans. They function as essential mechanisms that direct how growth and metabolism adapt to nutritional cues. mTOR is a Ser/Thr protein kinase, while the Vps15/Vps34 complex is a lipid kinase with phosphatidylinositol 3-kinase activity (class III PI3K). The transduction mechanisms triggered by mTOR and class III PI3K are complex. In mammalian cells, both kinases are engaged in multiple complexes that have different localization, targets and sensitivities to upstream signals, like nutrients and insulin. We have contributed to demonstrate that this crosstalk and differential regulation may explain many physiological responses to nutrition. For instance, why nutrients and insulin are synergistic for cell growth, though nutrients cause resistance to the metabolic action of insulin. Or why insulin inhibits autophagy, though stimulates receptor trafficking. During the past fifteen years we have generated and characterized a wide panel of mouse mutants in the mTOR and class III PI3K pathways. We were involved in revealing unique and interesting phenotypes that increased our knowledge of mTOR/class III PI3K roles in pathophysiology: mutants with small cells (Pende et al., Nature, 2000; Ohanna et al., Nature Cell Biol, 2005), mutants resistant to tumorigenesis in specific tissues and after specific oncogenic insults (Alliouachene et al., JCI, 2008; Panasyuk et al., Nature Comm., 2012; Patitucci et al., JCI, 2017), mutants with muscle disease (Risson et al., JCB, 2009; Nemazanyy et al., EMBO Mol Med, 2013), mutants mimicking caloric restriction and promoting longevity (Aguilar et al., Cell Metabolism, 2007; Barilari et al., EMBO J, 2017), mutants with altered insulin action (Nemazanyy et al., Nature Comm., 2015; Treins et al., Mol Cel Biol, 2012). I will present our progress on the molecular mechanisms of cell size control and organismal longevity. I will also detail our efforts to understand rare human genetic diseases that arise from pathological changes in the activity of the mTOR/ class III PI3K pathways or that may benefit from therapeutical intervention on these pathways. These diseases include Tuberous Sclerosis Complex and lysosomal storage diseases.
Abstract:
In metazoans, nutrient and growth factor availability control cell number, size and metabolic homeostasis. We investigate the specific programs underlying these responses, and their coordination by signal transduction mechanisms.We focus on two nutrient signal transduction pathways, the mTOR (mammalian Target Of Rapamycin) and the Vps15/Vps34 complex (Vacuolar Protein Sorting15/34). These ancient pathways are present in every eukaryotic cell, from unicellular organisms like yeast to humans. They function as essential mechanisms that direct how growth and metabolism adapt to nutritional cues. mTOR is a Ser/Thr protein kinase, while the Vps15/Vps34 complex is a lipid kinase with phosphatidylinositol 3-kinase activity (class III PI3K). The transduction mechanisms triggered by mTOR and class III PI3K are complex. In mammalian cells, both kinases are engaged in multiple complexes that have different localization, targets and sensitivities to upstream signals, like nutrients and insulin. We have contributed to demonstrate that this crosstalk and differential regulation may explain many physiological responses to nutrition. For instance, why nutrients and insulin are synergistic for cell growth, though nutrients cause resistance to the metabolic action of insulin. Or why insulin inhibits autophagy, though stimulates receptor trafficking. During the past fifteen years we have generated and characterized a wide panel of mouse mutants in the mTOR and class III PI3K pathways. We were involved in revealing unique and interesting phenotypes that increased our knowledge of mTOR/class III PI3K roles in pathophysiology: mutants with small cells (Pende et al., Nature, 2000; Ohanna et al., Nature Cell Biol, 2005), mutants resistant to tumorigenesis in specific tissues and after specific oncogenic insults (Alliouachene et al., JCI, 2008; Panasyuk et al., Nature Comm., 2012; Patitucci et al., JCI, 2017), mutants with muscle disease (Risson et al., JCB, 2009; Nemazanyy et al., EMBO Mol Med, 2013), mutants mimicking caloric restriction and promoting longevity (Aguilar et al., Cell Metabolism, 2007; Barilari et al., EMBO J, 2017), mutants with altered insulin action (Nemazanyy et al., Nature Comm., 2015; Treins et al., Mol Cel Biol, 2012). I will present our progress on the molecular mechanisms of cell size control and organismal longevity. I will also detail our efforts to understand rare human genetic diseases that arise from pathological changes in the activity of the mTOR/ class III PI3K pathways or that may benefit from therapeutical intervention on these pathways. These diseases include Tuberous Sclerosis Complex and lysosomal storage diseases.
Links
Practical information
- Informed public
- Free
Organizer
- Prof. Lluis Fajas (UNIL), Prof. Kei Sakamoto (NIHS) and Prof. Kristina Schoonjans (EPFL)
Contact
- Prof. Lluis Fajas (UNIL) - [email protected]