TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis.
The evolutionarily conserved Orm1 and Orm2 proteins mediate sphingolipid homeostasis. However, the homologous Orm proteins and the signaling pathways modulating their phosphorylation and function are incompletely characterized. Here we demonstrate that inhibition of nutrient-sensitive target of rapamycin complex 1 (TORC1) stimulates Orm phosphorylation and synthesis of complex sphingolipids in Saccharomyces cerevisiae. TORC1 inhibition activates the kinase Npr1 that directly phosphorylates and activates the Orm proteins. Npr1-phosphorylated Orm1 and Orm2 stimulate de novo synthesis of complex sphingolipids downstream of serine palmitoyltransferase. Complex sphingolipids in turn stimulate plasma membrane localization and activity of the nutrient scavenging general amino acid permease 1. Thus activation of Orm and complex sphingolipid synthesis upon TORC1 inhibition is a physiological response to starvation.
Biozentrum, University of Basel, 4056 Basel, Switzerland.
Mitsugu
M
Shimobayashi
Wolfgang
W
Oppliger
Suzette
S
Moes
Paul
P
Jenö
Michael N
MN
Hall
D026905:Amino Acid Transport Systems / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D006706:Homeostasis; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051102:Serine C-Palmitoyltransferase / Q000235:genetics; D013107:Sphingolipids / Q000096:biosynthesis*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism*
D026905:Amino Acid Transport Systems; C548539:Orm1 protein, S cerevisiae; C548540:Orm2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D013107:Sphingolipids; C561842:TORC1 protein complex, S cerevisiae; D014157:Transcription Factors; C066958:NPR1 protein, S cerevisiae; D051102:Serine C-Palmitoyltransferase; D011494:Protein Kinases