The yeast H⁺-ATPase Pma1 promotes Rag/Gtr-dependent TORC1 activation in response to H⁺-coupled nutrient uptake.

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.