Reciprocal Regulation of Target of Rapamycin Complex 1 and Potassium Accumulation

Abstract

Edited by Thomas SöllnerThe proper maintenance of potassium homeostasis is crucial for cell viability. Among the major determinants of potassium uptake in the model organism Saccharomyces cerevisiae are the Trk1 high affinity potassium transporter and the functionally redundant Hal4 (Sat4) and Hal5 protein kinases. These kinases are required for the plasma membrane accumulation of not only Trk1 but also several nutrient permeases. Here, we show that overexpression of the target of rapamycin complex 1 (TORC1) effector NPR1 improves hal4 hal5 growth defects by stabilizing nutrient permeases at the plasma membrane. We subsequently found that internal potassium levels and TORC1 activity are linked. Specifically, growth under limiting potassium alters the activities of Npr1 and another TORC1 effector kinase, Sch9; hal4 hal5 and trk1 trk2 mutants display hypersensitivity to rapamycin, and reciprocally, TORC1 inhibition reduces potassium accumulation. Our results demonstrate that in addition to carbon and nitrogen, TORC1 also responds to and regulates potassium fluxes.

TOR complex 1 regulates the yeast plasma membrane proton pump and pH and potassium homeostasis

“…The mechanism is elusive because it does not involve the known phosphorylation sites of the enzyme. It has recently been described that rapamycin decreases K + accumulation in yeast cells independently of the Trk1 and Trk2 high-affinity transporters [52]. Our results suggest that this effect could be mediated by the inhibition of Pma1 by rapamycin.…”

“…One important aspect of these findings is that there is a reciprocal regulation between TORC1 and the H + and K + transport systems. This was first described for the TORC1‐K + pair, where a decrease in K + accumulation activates TORC1 and inactivation of TORC1 decreases K + accumulation . In the case of H + pumping it has been described that activation of Pma1 by glucose increases TORC1 activity and that this effect is mediated by an increase in intracellular pH .…”

Monovalent cation transporters at the plasma membrane in yeasts

“…The meaning of newly identified and quite complex regulatory processes remains to be elucidated. The relationship between phosphate metabolism and potassium homeostasis, in which the PHO pathway and the 14‐3‐3 proteins encoded by BMH1,2 are involved (Canadell, González, Casado, & Ariño, ; Teunissen, Crooijmans, Teunisse, & van Heusden, ), or the role of the Target of Rapamycin Complex 1 (TORC1) effector NPR1 improving hal4 hal5 growth defects, which somehow links TORC1 to carbon, nitrogen, and now, to potassium fluxes (Mahmoud et al, ; Primo, Ferri‐Blázquez, Loewith, & Yenush, ), deserves more attention.…”

A Snf1-related nutrient-responsive kinase antagonizes endocytosis in yeast

“…Importantly, Npr1 is thought to antagonize endocytosis at the level of specific Rsp5 adaptor proteins, including Art1, Bul1, and Bul2, and therefore regulate a specific subset of endocytic cargo [27,30,31]. Surprisingly, previous reports indicate that overexpression of Npr1 improves hal mutant growth defects through stabilization of nutrient transporters at the PM [94], suggesting that Npr1 may compensate for some Hal functions. However, our data indicates that Hal kinases do not function to regulate Art1 phosphorylation or localization, suggesting that Hal kinases and Npr1 function via distinct mechanisms.…”