Pib2-Dependent Feedback Control of the TORC1 Signaling Network by the Npr1 Kinase

To adjust cell growth and metabolism according to environmental conditions, the conserved TORC1 signaling network controls autophagy, protein synthesis, and turnover. Here, we dissected the signals controlling phosphorylation and activity of the TORC1-effector kinase Npr1, involved in tuning the plasma membrane permeability to nitrogen sources. By evaluating a role of pH as a signal, we show that, although a transient cytosolic acidification accompanies nitrogen source entry and is correlated to a rapid TORC1-dependent phosphorylation of Npr1, a pH drop is not a prerequisite for TORC1 activation. We show that the Gtr1/Gtr2 and Pib2 regulators of TORC1 both independently and differently contribute to regulate Npr1 phosphorylation and activity. Finally, our data reveal that Npr1 mediates nitrogen-dependent phosphorylation of Pib2, as well as a Pib2-dependent inhibition of TORC1. This work highlights a feedback control loop likely enabling efficient downregulation and faster re-activation of TORC1 in response to a novel stimulating signal.