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Published on: September 28, 2018
Nte1p-mediated deacylation of phosphatidylcholine functionally interacts with Sec14p
J Pedro Fernández Murray1, Christopher R McMaster
1Atlantic Research Centre, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3H 4H7, Canada.
Sec14p protein regulates lipid homeostasis and secretion. Its absence is compensated by Sfh2p and Sfh4p, which alter phosphatidylcholine metabolism and choline transport, revealing Sec14p
Area of Science:
- * Cell Biology
- * Biochemistry
- * Molecular Genetics
Background:
- * Sec14p is an essential yeast protein regulating Golgi cargo secretion and lipid homeostasis.
- * Phosphatidylcholine (PC) synthesis via the CDP-choline (CDP-Cho) pathway is crucial for cell viability.
- * Nte1p is a phospholipase that degrades CDP-Cho-derived PC, producing glycerophosphocholine (GPCho).
Purpose of the Study:
- * To investigate the role of Sec14p in phosphatidylcholine (PC) metabolism and its relationship with Nte1p activity.
- * To understand how Sec14p homologs (Sfh2p, Sfh4p) compensate for the absence of Sec14p.
- * To elucidate the mechanisms by which Sfh2p and Sfh4p restore growth and secretion in sec14 mutants.
Main Methods:
- * In vivo measurements of PC turnover and GPCho accumulation in wild-type and mutant yeast strains.
- * Analysis of Nte1p and phospholipase D (Spo14p) activity under different genetic conditions.
- * Monitoring of choline (Cho) uptake and excretion in cells overexpressing Sec14p homologs.
Main Results:
- * Absence of Sec14p leads to altered PC metabolism, including Nte1p unresponsiveness and Spo14p activation.
- * Overexpression of Sfh2p and Sfh4p in sec14 mutants restores growth and secretion but not normal GPCho levels.
- * Sfh2p and Sfh4p modulate PC metabolism by controlling phosphocholine formation, limiting available choline, and promoting choline excretion.
- * Sec14p positively regulates Nte1p-mediated PC deacylation, enhancing Nte1p activity.
Conclusions:
- * Sec14p plays a dual role in mediating PC homeostasis and regulating Nte1p activity.
- * Sfh2p and Sfh4p compensate for Sec14p absence through novel mechanisms of PC metabolic control and choline transport.
- * Understanding these pathways offers insights into lipid homeostasis and cellular secretion regulation.
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