Abstract
The yeast Target of Rapamycin Complex 1 (TORC1) plays a central role in controlling growth. How amino acids and other nutrients stimulate its activity via the Rag/Gtr GTPases remains poorly understood. We here report that the signal triggering Rag/Gtr-dependent TORC1 activation upon amino-acid uptake is the coupled H+ influx catalyzed by amino-acid/H+ symporters. H+-dependent uptake of other nutrients, ionophore-mediated H+ diffusion, and inhibition of the vacuolar V-ATPase also activate TORC1. As the increase in cytosolic H+ elicited by these processes stimulates the compensating H+-export activity of the plasma membrane H+-ATPase (Pma1), we have examined whether this major ATP-consuming enzyme might be involved in TORC1 control. We find that when the endogenous Pma1 is replaced with a plant H+-ATPase, H+ influx or increase fails to activate TORC1. Our results show that H+ influx coupled to nutrient uptake stimulates TORC1 activity and that Pma1 is a key actor in this mechanism.
Highlights
The Target of Rapamycin Complex 1 (TORC1) plays a pivotal role in controlling cell growth in probably all eukaryotic organisms
Thanks to isolation of a Gap1 mutant insensitive to this TORC1-dependent ubiquitylation, we have shown that substrate transport by Gap1 can trigger Ub-dependent endocytosis and degradation of this transporter (Ghaddar et al, 2014b)
Our study shows that what triggers this activation is the H+ influx coupled to transport by H+/amino-acid symporters
Summary
The Target of Rapamycin Complex 1 (TORC1) plays a pivotal role in controlling cell growth in probably all eukaryotic organisms It operates by integrating upstream signals such as growth factors (GFs) and nutrients to modulate, by phosphorylation, multiple downstream effectors, mostly proteins involved in anabolic processes (e.g. protein synthesis, ribosome biogenesis) or catabolic processes (e.g. autophagy, bulk endocytosis of plasma membrane transporters) (Gonzalez and Hall, 2017; Powis and De Virgilio, 2016; Saxton and Sabatini, 2017). Recent studies have aimed to identify these GAPs and GEFs and their upstream regulators and to better understand how these factors are controlled in response to variations in the cytosolic concentrations of amino acids and/or to their transport across the plasma or lysosomal membrane (Gonzalez and Hall, 2017; Powis and De Virgilio, 2016; Saxton and Sabatini, 2017).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
