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Published on: March 20, 2016
Cell wall integrity MAPK pathway is essential for lipid homeostasis
Lilia R Nunez1, Stephen A Jesch, Maria L Gaspar
1Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853, USA.
The yeast cell wall integrity pathway is crucial for maintaining lipid homeostasis, especially under inositol-deficient conditions. This pathway regulates phospholipid synthesis and turnover, preventing lipid accumulation and ensuring cell viability.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- The yeast cell wall integrity mitogen-activated protein kinase (MAPK) pathway is a highly conserved signaling cascade.
- This pathway is known to regulate cellular responses to stress affecting the cell wall and membrane.
Purpose of the Study:
- To investigate the role of the cell wall integrity pathway in regulating lipid metabolism under specific growth conditions.
- To determine the essentiality of this pathway for yeast viability when membrane phospholipid synthesis and turnover are altered.
Main Methods:
- Analysis of yeast mutants defective in the cell wall integrity pathway.
- Assessment of gene expression, including Opi1p-regulated genes like INO1.
- Phosphorylation studies of Mpk1p (mitogen-activated protein kinase 1).
- Lipid profiling to identify accumulated or aberrant lipids.
- Genetic analysis using gene overexpression, specifically phospholipase genes.
Main Results:
- The cell wall integrity pathway is activated and essential for viability when phosphatidylinositol and phosphatidylcholine metabolism is altered.
- Mutants exhibit choline-sensitive inositol auxotrophy and defects in lipid metabolism, including accumulation of phosphatidylcholine, diacylglycerol, triacylglycerol, and sterols.
- Mpk1p activation stimulates transcription of Mpk1p and Rlm1p targets under these conditions.
- Overexpression of NTE1 phospholipase B suppresses the auxotrophy, indicating its role in lipid turnover.
Conclusions:
- An intact cell wall integrity pathway is required for maintaining lipid homeostasis in yeast.
- This pathway plays a critical role in regulating phospholipid synthesis, turnover, and overall lipid metabolism, particularly under inositol limitation.
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