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

Mitsugu Shimobayashi1, Wolfgang Oppliger, Suzette Moes

  • 1Biozentrum, University of Basel, 4056 Basel, Switzerland.

Molecular Biology of the Cell
|February 1, 2013
PubMed

Insights

Nutrient-sensitive target of rapamycin complex 1 (TORC1) inhibition activates the kinase Npr1, which phosphorylates Orm proteins. This stimulates sphingolipid synthesis, a starvation response in yeast.

Area of Science:

  • Cellular biology
  • Biochemistry
  • Molecular biology

Background:

  • Orm1 and Orm2 proteins are crucial for sphingolipid homeostasis but their regulation is not fully understood.
  • Signaling pathways affecting Orm protein phosphorylation and function require further characterization.

Purpose of the Study:

  • To investigate the role of nutrient-sensitive target of rapamycin complex 1 (TORC1) signaling in regulating Orm proteins.
  • To elucidate the mechanism by which TORC1 inhibition impacts sphingolipid synthesis and function.

Main Methods:

  • Utilized Saccharomyces cerevisiae as a model organism.
  • Investigated protein phosphorylation using biochemical assays.
  • Analyzed sphingolipid synthesis pathways.
  • Examined protein localization and activity using cell biology techniques.

Main Results:

  • TORC1 inhibition leads to Orm protein phosphorylation and increased synthesis of complex sphingolipids.
  • The kinase Npr1 directly phosphorylates and activates Orm proteins upon TORC1 inhibition.
  • Activated Orm proteins stimulate de novo sphingolipid synthesis downstream of serine palmitoyltransferase.
  • Complex sphingolipids enhance the plasma membrane localization and activity of the general amino acid permease 1.

Conclusions:

  • TORC1 signaling pathway regulates Orm proteins and sphingolipid homeostasis in yeast.
  • Npr1-mediated phosphorylation of Orm proteins is a key step in response to nutrient starvation.
  • The Orm-sphingolipid pathway plays a vital role in nutrient scavenging during starvation.

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