Regulation of phospholipid synthesis in the yeast cki1Delta eki1Delta mutant defective in the Kennedy pathway. The Cho1-encoded phosphatidylserine synthase is regulated by mRNA stability.
In the yeast Saccharomyces cerevisiae, the most abundant phospholipid phosphatidylcholine is synthesized by the complementary CDP-diacylglycerol and Kennedy pathways. Using a cki1Delta eki1Delta mutant defective in choline kinase and ethanolamine kinase, we examined the consequences of a block in the Kennedy pathway on the regulation of phosphatidylcholine synthesis by the CDP-diacylglycerol pathway. The cki1Delta eki1Delta mutant exhibited increases in the synthesis of phosphatidylserine, phosphatidylethanolamine, and phosphatidylcholine via the CDP-diacylglycerol pathway. The increase in phospholipid synthesis correlated with increased activity levels of the CDP-diacylglycerol pathway enzymes phosphatidylserine synthase, phosphatidylserine decarboxylase, phosphatidylethanolamine methyltransferase, and phospholipid methyltransferase. However, other enzyme activities, including phosphatidylinositol synthase and phosphatidate phosphatase, were not affected in the cki1Delta eki1Delta mutant. For phosphatidylserine synthase, the enzyme catalyzing the committed step in the pathway, activity was regulated by increases in the levels of mRNA and protein. Decay analysis of CHO1 mRNA indicated that a dramatic increase in transcript stability was a major component responsible for the elevated level of phosphatidylserine synthase. These results revealed a novel mechanism that controls phospholipid synthesis in yeast.
Choi
Hyeon-Son
HS
Department of Food Science, Rutgers University, 65 Dudley Road, New Brunswick, NJ 08901, USA.
Sreenivas
Avula
A
Han
Gil-Soo
GS
Carman
George M
GM
D001669:Biochemical Phenomena; D001671:Biochemistry; D015152:Blotting, Northern; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000096:biosynthesis*; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D015151:Immunoblotting; D008954:Models, Biological; D009154:Mutation; D010713:Phosphatidylcholines / Q000096:biosynthesis; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D010718:Phosphatidylserines / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*; D013997:Time Factors
D003567:Cytidine Diphosphate Diglycerides; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; D012333:RNA, Messenger; C483858:phosphatidylethanolamine; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase