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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
Summary
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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