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TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis


Shimobayash, Mitsugu; Oppliger, Wolfgang; Moes, Suzette; Jenö, Paul; Hall, Michael N (2013). TORC1-regulated protein kinase Npr1 phosphorylates Orm to stimulate complex sphingolipid synthesis. Molecular Biology of the Cell, 24:870-881.

Abstract

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.

Abstract

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:Special Collections > SystemsX.ch
Special Collections > SystemsX.ch > Research, Technology and Development Projects > YeastX
Special Collections > SystemsX.ch > Research, Technology and Development Projects
Dewey Decimal Classification:570 Life sciences; biology
Language:English
Date:March 2013
Deposited On:26 Jun 2013 08:18
Last Modified:21 Nov 2017 16:45
Publisher:American Society for Cell Biology
ISSN:1059-1524
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1091/mbc.E12-10-0753

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