Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 13, Pages 5851-5856Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0911617107
Keywords
membrane biogenesis; sphingolipid synthesis; unfolded protein response
Categories
Funding
- Swiss National Science Foundation [3100A0_120650]
- National Institutes of Health [GM 58212]
Ask authors/readers for more resources
Yeast members of the ORMDL family of endoplasmic reticulum (ER) membrane proteins play a central role in lipid homeostasis and protein quality control. In the absence of yeast Orm1 and Orm2, accumulation of long chain base, a sphingolipid precursor, suggests dysregulation of sphingolipid synthesis. Physical interaction between Orm1 and Orm2 and serine palmitoyltransferase, responsible for the first committed step in sphingolipid synthesis, further supports a role for the Ormproteins in regulatingsphingolipid synthesis. Phospholipid homeostasis is also affected in orm1. orm2. cells: the cells are inositol auxotrophs withimpaired transcriptional regulation of genes encoding phospholipid biosynthesis enzymes. Strikingly, impaired growth of orm1. orm2. cells is associated with constitutive unfolded protein response, sensitivity to stress, and slow ER-to-Golgi transport. Inhibition of sphingolipid synthesis suppresses orm1. orm2. phenotypes, including ER stress, suggesting that disrupted sphingolipid homeostasis accounts for pleiotropic phenotypes. Thus, the yeast Orm proteins control membrane biogenesis by coordinating lipid homeostasis with protein quality control.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available