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Fluorescence-Based Measurements of Phosphatidylserine/Phosphatidylinositol 4-Phosphate Exchange Between Membranes
Published on: March 14, 2021
Regulation of sphingolipid synthesis through Orm1 and Orm2 in yeast.
Ming Liu1, Chunjuan Huang, Surendranath R Polu
1Division of Metabolism, Endocrinology, and Diabetes, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Journal of Cell Science
|February 14, 2012
Summary
Yeast Orm1 and Orm2 regulate sphingolipid synthesis, a process targeted by TOR signaling and responsive to ER stress. Their absence constitutively activates the unfolded protein response (UPR), indicating coordinated regulation.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- Sphingolipids are vital membrane components and signaling molecules.
- Yeast Orm1 and Orm2 proteins regulate serine palmitoyltransferase, controlling sphingolipid synthesis.
- TOR signaling influences cell growth based on nutrient availability.
Purpose of the Study:
- To investigate the regulation of sphingolipid synthesis by TOR signaling and ER stress.
- To elucidate the roles of Orm1 and Orm2 in these regulatory pathways.
- To understand the interplay between sphingolipid synthesis and the unfolded protein response (UPR).
Main Methods:
- Analysis of Orm1 phosphorylation in relation to TOR signaling and the Tap42-phosphatase complex.
- Assessment of Orm2 protein levels under ER stress conditions (tunicamycin, DTT).
- Investigation of UPR activation in yeast lacking Orm proteins.
Main Results:
- Orm1 phosphorylation, regulated by TOR signaling, impacts sphingolipid synthesis.
- Orm2 protein levels increase during ER stress, repressing sphingolipid synthesis.
- Absence of Orm proteins leads to constitutive UPR activation, linked to lipid dysregulation.
Conclusions:
- Sphingolipid synthesis is a target of TOR signaling and is modulated by ER stress via Orm proteins.
- Sphingolipid homeostasis and the UPR are coordinately regulated.
- Lipid dysregulation in Orm-deficient cells may signal ER stress from the plasma membrane.
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