Nte1p-mediated Deacylation of Phosphatidylcholine Functionally Interacts with Sec14p

Deciphering the function of the essential yeast Sec14p protein has revealed a regulatory interface between cargo secretion from Golgi and lipid homeostasis. Abrogation of the CDP-choline (CDP-Cho) pathway for phosphatidylcholine (PC) synthesis allows for life in the absence of the otherwise essential Sec14p. Nte1p, the product of open reading frame YML059c, is an integral membrane phospholipase against CDP-Cho-derived PC producing intracellular glycerophosphocholine (GPCho) and free fatty acids. We monitored Nte1p activity through in vivo PC turnover measurements and observed that intracellular GPCho accumulation is decreased in a sec14ts strain shifted to 37 °C in 10 mm choline (Cho)-containing medium compared with a Sec14p-proficient strain. Overexpression of two Sec14p homologs Sfh2p and Sfh4p in sec14ts cells restored secretion and growth at the restrictive temperature but did not restore GPCho accumulation. Instead, newly synthesized PC was degraded by phospholipase D (Spo14p). Similar analysis performed in a sec14Δ background confirmed these observations. These results imply that the ability of Sfh2p and Sfh4p to restore secretion and growth is not through a shared function with Sec14p in the regulation of PC turnover via Nte1p. Furthermore, our analyses revealed a profound alteration of PC metabolism triggered by the absence of Sec14p: Nte1p unresponsiveness, Spo14p activation, and deregulation of Pct1p. Sfh2p- and Sfh4p-overexpressing cells coped with the absence of Sec14p by controlling the rate of phosphocholine formation, limiting the amount of Cho available for this reaction, and actively excreting Cho from the cell. Increased Sfh4p also significantly reduced the uptake of exogenous Cho. Beyond the new PC metabolic control features we ascribe to Sfh2p and Sfh4p we also describe a second role for Sec14p in mediating PC homeostasis. Sec14p acts as a positive regulator of Nte1p-mediated PC deacylation with the functional consequence of increased Nte1p activity increasing the permissive temperature for the growth of sec14ts cells. Deciphering the function of the essential yeast Sec14p protein has revealed a regulatory interface between cargo secretion from Golgi and lipid homeostasis. Abrogation of the CDP-choline (CDP-Cho) pathway for phosphatidylcholine (PC) synthesis allows for life in the absence of the otherwise essential Sec14p. Nte1p, the product of open reading frame YML059c, is an integral membrane phospholipase against CDP-Cho-derived PC producing intracellular glycerophosphocholine (GPCho) and free fatty acids. We monitored Nte1p activity through in vivo PC turnover measurements and observed that intracellular GPCho accumulation is decreased in a sec14ts strain shifted to 37 °C in 10 mm choline (Cho)-containing medium compared with a Sec14p-proficient strain. Overexpression of two Sec14p homologs Sfh2p and Sfh4p in sec14ts cells restored secretion and growth at the restrictive temperature but did not restore GPCho accumulation. Instead, newly synthesized PC was degraded by phospholipase D (Spo14p). Similar analysis performed in a sec14Δ background confirmed these observations. These results imply that the ability of Sfh2p and Sfh4p to restore secretion and growth is not through a shared function with Sec14p in the regulation of PC turnover via Nte1p. Furthermore, our analyses revealed a profound alteration of PC metabolism triggered by the absence of Sec14p: Nte1p unresponsiveness, Spo14p activation, and deregulation of Pct1p. Sfh2p- and Sfh4p-overexpressing cells coped with the absence of Sec14p by controlling the rate of phosphocholine formation, limiting the amount of Cho available for this reaction, and actively excreting Cho from the cell. Increased Sfh4p also significantly reduced the uptake of exogenous Cho. Beyond the new PC metabolic control features we ascribe to Sfh2p and Sfh4p we also describe a second role for Sec14p in mediating PC homeostasis. Sec14p acts as a positive regulator of Nte1p-mediated PC deacylation with the functional consequence of increased Nte1p activity increasing the permissive temperature for the growth of sec14ts cells. Lipid homeostasis is fulfilled through the coordinated synthesis, degradation, and trafficking of the lipid constituents of biological membranes. Many biological processes such as vesicle formation, protein trafficking, and lipid signaling are dependent on proper lipid content at particular membrane locations, and many cellular pathophysiological situations are associated with perturbations in lipid homeostasis (1McMaster C.R. Jackson T.R. Daum G. Lipid Metabolism and Membrane Biogenesis. 6. Springer-Verlag, Berlin2004: 5-88Google Scholar). Deciphering the function of the Saccharomyces cerevisiae Sec14p protein has uncovered a regulatory interface between cargo secretion from the Golgi and lipid metabolism (2Routt S.M. Bankaitis V.A. Biochem. Cell Biol. 2004; 82: 254-262Crossref PubMed Scopus (53) Google Scholar, 3McMaster C.R. Biochem. Cell Biol. 2001; 79: 681-692Crossref PubMed Scopus (70) Google Scholar). Sec14p is an essential soluble protein possessing in vitro phosphatidylinositol (PI) 1The abbreviations used are: PI, phosphatidylinositol; CDP-Cho, CDP-choline; Cho, choline; GPCho, glycerophosphocholine; NTE or Nte, neuropathy target esterase; ORF, open reading frame; PC, phosphatidylcholine; P-Cho, phosphocholine; Pct1p, CTP:phosphocholine cytidylyltransferase./phosphatidylcholine (PC) transfer activity. Sec14p is located primarily in the cytoplasm, and it has been observed to associate with Golgi membranes presumably through its phospholipid binding ability (4Cleves A.E. McGee T.P. Whitters E.A. Champion K.M. Aitken J.R. Dowhan W. Goebl M. Bankaitis V.A. Cell. 1991; 64: 789-800Abstract Full Text PDF PubMed Scopus (286) Google Scholar). The lethality associated with Sec14p dysfunction or absence can be overcome by inactivating mutations in each of the three structural genes of the CDP-choline (CDP-Cho) pathway for PC biosynthesis (4Cleves A.E. McGee T.P. Whitters E.A. Champion K.M. Aitken J.R. Dowhan W. Goebl M. Bankaitis V.A. Cell. 1991; 64: 789-800Abstract Full Text PDF PubMed Scopus (286) Google Scholar). In yeast PC can also be synthesized through the methylation pathway where phosphatidylethanolamine is methylated sequentially yielding PC (5Howe A.G. McMaster C.R. Biochim. Biophys. Acta. 2001; 1534: 65-77Crossref PubMed Scopus (27) Google Scholar, 6Howe A.G. Zaremberg V. McMaster C.R. J. Biol. Chem. 2002; 277: 44100-44107Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar). Abrogation of the CDP-Cho pathway functionally complements the absence of Sec14p (2Routt S.M. Bankaitis V.A. Biochem. Cell Biol. 2004; 82: 254-262Crossref PubMed Scopus (53) Google Scholar, 4Cleves A.E. McGee T.P. Whitters E.A. Champion K.M. Aitken J.R. Dowhan W. Goebl M. Bankaitis V.A. Cell. 1991; 64: 789-800Abstract Full Text PDF PubMed Scopus (286) Google Scholar, 5Howe A.G. McMaster C.R. Biochim. Biophys. Acta. 2001; 1534: 65-77Crossref PubMed Scopus (27) Google Scholar, 7Skinner H.B. McGee T.P. McMaster C.R. Bankaitis V.A. PubMed Scopus Google Scholar). was also that Sec14p to PC by an CTP:phosphocholine activity H.B. McGee T.P. McMaster C.R. Bankaitis V.A. PubMed Scopus Google the of the CDP-Cho pathway C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). Sec14p a in through this pathway H.B. McGee T.P. McMaster C.R. Bankaitis V.A. PubMed Scopus Google Scholar). genes that growth and secretion on the absence of Sec14p are and genes are also in lipid metabolism and the that the function of Sec14p with lipid homeostasis M. M. Bankaitis V.A. J. PubMed Scopus Google Scholar, M. J. Bankaitis V.A. J. Cell Biol. 2002; PubMed Scopus Google Scholar, Bankaitis V.A. Biol. Cell. PubMed Scopus Google Scholar). and to the and protein in vitro transfer activity but not the PC transfer activity of Sec14p. to PC, the of Sfh2p and but not of the growth in the absence of Sec14p S.M. M. M. Bankaitis V.A. Biol. Cell. PubMed Scopus Google Scholar, M. M. Daum G. J. Biochem. PubMed Scopus Google Scholar, M. J. Biochem. 2004; PubMed Scopus Google Scholar). and D been in yeast with activity against D a producing and choline The PC phospholipase D in yeast is a soluble protein primarily in the but with the to to cellular membranes for V.A. J. J. J. Cell Biol. 2002; PubMed Scopus Google Scholar, V.A. J. J. PubMed Scopus Google Scholar, V. McMaster C.R. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biochim. Biophys. Acta. PubMed Scopus Google Scholar). Spo14p has an essential function for but is for of Sec14p function Spo14p and the ability of the genes can the essential function of Sec14p is dependent on functional Spo14p V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Bankaitis V.A. PubMed Scopus Google Scholar). glycerophosphocholine (GPCho) and free fatty acids. genes for phospholipase been in cerevisiae protein are located at the membrane and the PubMed Scopus Google Scholar, M. J. Biol. Chem. Full Text PDF PubMed Google Scholar). the activity for PC deacylation at the membrane with its of GPCho the J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google a PC activity for the of intracellular activity was by the of Cho in the medium or the growth temperature was to 37 was that the of the of Cho and of the of temperature on the activity dependent on an CDP-Cho pathway for PC The yeast open reading frame was to for this and the protein has to the neuropathy target protein J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). the and yeast are located in the and against a of a of the role by Sec14p in protein secretion and but a Sec14p the lipid of cellular for cargo We metabolic and that as it is the yeast of neuropathy target functionally with Sec14p and also for Sec14p and its homologs Sfh2p and Sfh4p in the regulation of PC synthesis and and from was from from and yeast and used in Scholar). The yeast used in this are in at °C in medium as for The was by from the in The was the and its the was by at the and the of the and the of the The from the and from the The the the of the and the the control of the a by Bankaitis of at S.M. M. M. Bankaitis V.A. Biol. Cell. PubMed Scopus Google Scholar). The of the the was to by in its a the and its regulatory The was by two by as and used to a of its and the of the its and used to a the of the and of the and by the used in this in a new used for the of the and in a new of PC yeast cells in medium the for growth with and in medium of for at in and in medium 10 mm Cho at or 37 at and cells by The and the cells to analysis and lipid as uptake was the the cells at the of the to in medium the for growth at and choline activity was as with the with and in medium 10 was to for and at °C C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). was for the uptake was by the of an of 10 mm 10 mm and mm Cho. through and with of mm Cho. The to and the associated was by PC yeast at °C at for in and in medium 10 at °C A.G. Zaremberg V. McMaster C.R. J. Biol. Chem. 2002; 277: 44100-44107Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, V. McMaster C.R. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). at the for analysis and lipid of cells at for at with in of and and for at °C a of The with of and and of and of and to the to in the by on the in the in a of A.G. Zaremberg V. McMaster C.R. J. Biol. Chem. 2002; 277: 44100-44107Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar, V. McMaster C.R. J. Biol. Chem. 2002; 277: Full Text Full Text PDF PubMed Scopus Google Scholar). with a and the for was on the of in intracellular or Cho cells in of medium at °C in and with a of mm mm and mm The metabolic by three of cells a of of and at °C and of by a of with on an between at °C the was to a new and the with of and of and and of The for 10 at and at for 10 of the was and to interface cellular was and an of was for lipid The was through a of with C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). Cho in the was from the to and by at for 10 The of Cho in of was the choline PubMed Scopus Google Scholar). of Cho from each cellular was on the of in the was the J. Biol. Chem. Full Text PDF PubMed Google and lipid as by and J. Biol. Chem. Full Text PDF PubMed Google Scholar). GPCho to product of the yeast is to neuropathy target and is for PC synthesized through the CDP-Cho pathway producing intracellular GPCho and free fatty J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). the of the for this activity was on its with the neuropathy target we and Nte1p as the for the and its protein activity was to with of the synthesis of PC by the of exogenous Cho or of temperature J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). a strain and its we performed analysis of PC with for at and the was the of 10 mm Cho at or 37 °C The analysis of from and intracellular as as medium the in revealed that the strain did not intracellular GPCho the of 10 mm Cho at or 37 The strain a amount of intracellular GPCho at the of the increased the at °C and the at 37 is with that Nte1p is the it is not for PC synthesized through the CDP-Cho pathway that to an accumulation of intracellular GPCho J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). The amount of Cho from the strain was the amount in the medium of the strain the was performed at 37 to PC this increased amount of Cho did not for the absence of intracellular GPCho in the strain of the was associated with PC of in the strain compared with of the with PC in the strain at the Cho uptake the as as Cho measurements C.R. J. Biol. Chem. Full Text PDF PubMed Google performed not that the strain Cho at the rate as the strain the at on the for a role for Sec14p in the CDP-Cho pathway for PC biosynthesis to from Golgi membranes (4Cleves A.E. McGee T.P. Whitters E.A. Champion K.M. Aitken J.R. Dowhan W. Goebl M. Bankaitis V.A. Cell. 1991; 64: 789-800Abstract Full Text PDF PubMed Scopus (286) Google Scholar, McMaster C.R. Biol. Cell. 2001; PubMed Scopus Google Scholar, M. Bankaitis V.A. Biol. Cell. 2001; PubMed Scopus Google we role Nte1p in this a phospholipase against CDP-Cho-derived PC that is located in the Nte1p to features to control the of PC through the CDP-Cho pathway at that a functional between Nte1p and Sec14p we performed to the rate of PC turnover in the strain with a the a the V.A. M. Bankaitis V.A. Cell. Full Text Full Text PDF PubMed Scopus Google and Sec14p in vitro PC and transfer PC transfer but it is to transfer between and Sec14p in yeast not been The of of the the a performed with 10 mm Cho at 37 °C in the sec14ts background is these mm Cho at 37 is and Nte1p is the two and the metabolic of sec14ts cells is to of and in the of intracellular GPCho was observed in the strain at to The strain a rate of intracellular GPCho the but it was that observed in cells. In in the sec14ts strain the of associated with intracellular GPCho at the as the was be that at 37 °C the strain is in with the and at that Overexpression of Sfh2p and Sfh4p allows yeast to in the otherwise absence of a functional Sec14p S.M. M. M. Bankaitis V.A. Biol. Cell. PubMed Scopus Google Scholar). The for the absence of Sec14p by of Sfh4p is dependent on the of Spo14p the of via of Sfh2p S.M. M. M. Bankaitis V.A. Biol. Cell. PubMed Scopus Google Scholar). We performed analysis of PC turnover in the strain Sfh2p or Sfh4p from to Sfh2p- and Sfh4p-overexpressing to that to the sec14ts strain The of associated with intracellular GPCho did not an the for the and These results that reduced intracellular GPCho accumulation is to the absence of a functional Sec14p and not to the lethality from its Furthermore, these results imply that the ability of Sfh2p and Sfh4p to restore secretion and growth is not through a shared function with Sec14p in the regulation of PC The of associated with increased for the sec14ts strain and for the sec14ts or is that of Sec14p of Furthermore, in Spo14p activity is an essential to overcome the absence of a functional with the of of S.M. M. M. Bankaitis V.A. Biol. Cell. PubMed Scopus Google Scholar). is to a of Cho in cells compared with cells with sec14ts The of Cho between these Spo14p of the a amount of the at the in the of associated with each the in of the role of Sec14p and its homologs Sfh2p and Sfh4p on the regulation of PC turnover we performed where the temperature to 37 °C was to of function of Sec14p via of a sec14ts sec14Δ or on and or on by of sec14Δ at and 37 °C or on or or on and growth in medium We the of a performed with 10 mm Cho at °C and of the The associated with phosphocholine decreased as it was to CDP-Cho and to PC the the amount of intracellular GPCho the associated with PC at the and of PC turnover to each from to and associated with intracellular GPCho was the and a amount of was in the associated with Cho The of and that PC through Spo14p to of free Cho the growth medium and that the activity of Nte1p was reduced in the and in the of 10 mm Cho, a that PC turnover by this as the metabolic of the and Cho and intracellular Cho content in rate was for cells in medium at uptake was performed in cells in medium 10 and uptake was and the cells by on and the associated was by the of two performed in Cho content was in yeast cells at °C to in lipid the and through a The amount of Cho in the was the of Cho Cho rate was for cells in medium at Cho uptake was performed in cells in medium 10 and uptake was and the cells by on and the associated was by the of two performed in Cho content was in yeast cells at °C to in lipid the and through a The amount of Cho in the was the of in a new a was performed but the temperature of the medium was to 37 an increased of associated with intracellular GPCho was for each of the compared with the was performed at °C intracellular GPCho temperature is a of Nte1p activity J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar, J. Biol. Chem. 2004; Full Text Full Text PDF PubMed Scopus Google Scholar). and a rate of GPCho accumulation the and cells did an in intracellular GPCho to the the associated with this to of the in the and In the of associated with intracellular GPCho in cells decreased at and In an the intracellular GPCho accumulation observed in the sec14Δ background at 37 °C in the sec14ts background at the temperature The of Cho and GPCho in the at 37 °C did not significantly from observed the was performed at °C and PC Metabolism in sec14Δ be the of the absence of Sec14p on PC the by Sfh2p- and Sfh4p-overexpressing cells the at °C was reduced compared with the by and of in uptake was not observed the was performed in a sec14ts background at the permissive temperature of °C of the in Cho uptake in Sfh2p- and Sfh4p-overexpressing cells in a sec14Δ background the of in the activity of the Cho and Cho uptake measurements performed C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). The rate of Cho uptake was this for The and of Cho uptake In cells the activity of the was in choline activity was reduced to in cells. of Sfh2p and Sfh4p in a Sec14p-proficient background on the amount of Cho the and the of the at the of the for of the it that Sec14p can its two homologs on Cho uptake and PC synthesis through the CDP-Cho this the activity of the Cho was in and in a sec14ts background two growth at °C or at 37 °C These three Cho at at at the restrictive temperature for the sec14ts the activity of the Cho in and cells was reduced to and that of cells uptake in uptake uptake 37 Cho Cho in a new that an Cho was associated with a from as the to choline the regulator for PC synthesis C.R. J. Biol. Chem. Full Text PDF PubMed Google Scholar). cellular Cho content was in yeast and we the from the in to the regulatory of choline in these cells. The for and cells at the at and 37 °C from for the and and the of the this is for and that in cells the CDP-Cho pathway is at the by Pct1p. the decreased as the of was and the activity of Cho was this was at 37 a that through this pathway A.G. Zaremberg V. McMaster C.R. J. Biol. Chem. 2002; 277: 44100-44107Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar, J. Biol. Chem. 2001; Full Text Full Text PDF PubMed Scopus Google Scholar). the in and cells at the of the that in cells the control of the at the was not and is with the that Sec14p the CDP-Cho pathway by the this is Sec14p and our that and cells are of PC synthesis at this for and cells the was but these not the of two as the Instead, at and the associated with Cho and but The Cho of the medium the that the associated with intracellular Cho at been from Cho by Spo14p and from the with the Cho of the and These to that activity for Cho and observed the at and 37 °C for and cells was the of the intracellular of Cho through a turnover of PC by Spo14p with reduced uptake of Cho from the medium the that Sfh2p- and Sfh4p-overexpressing cells decreased regulation of PC synthesis we performed choline for to with the in sec14Δ cells we observed that the at in and in Sfh2p- and Sfh4p-overexpressing cells the for the not We observed that and cells Cho against 10 mm the of Cho with an intracellular Cho we Cho in and cells in a sec14Δ Sfh2p- and Sfh4p-overexpressing cells the amount of Cho in Sec14p-proficient cells Overexpression of Nte1p the of the sec14ts metabolic a functional between Sec14p and Nte1p, an integral that of PC through the CDP-Cho pathway to free fatty and metabolic results are with a that increased Nte1p function the of of function of Sec14p. this Nte1p was from a in a sec14ts strain. cells at a temperature for the strain with did not We that Nte1p, an integral membrane phospholipase that a for PC from the CDP-Cho functionally with Sec14p. Pct1p, Sec14p is from its control the through the CDP-Cho pathway on the of Cho and H.B. McGee T.P. McMaster C.R. Bankaitis V.A. PubMed Scopus Google Scholar, V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Bankaitis V.A. PubMed Scopus Google Scholar, McMaster C.R. Biol. Cell. 2001; PubMed Scopus Google Scholar, M. Bankaitis V.A. Biol. Cell. 2001; PubMed Scopus Google Scholar). be that a PC content Nte1p an increased rate of PC is not the the that the accumulation of intracellular GPCho, the product of Nte1p Sec14p is Nte1p and are of Sec14p and an of in vitro transfer but for PC transfer activity V.A. M. Bankaitis V.A. Cell. Full Text Full Text PDF PubMed Scopus Google Scholar). Sec14p to PC, controlling the amount of PC from the CDP-Cho pathway at Sec14p this function by the rate of PC biosynthesis through the CDP-Cho pathway H.B. McGee T.P. McMaster C.R. Bankaitis V.A. PubMed Scopus Google and increasing its by Nte1p. with this role we observed that of Nte1p growth of sec14ts cells at the restrictive temperature of The PC turnover and Cho uptake measurements performed in sec14ts background that Sec14p a role controlling PC is not by the of Sfh2p or Sfh4p restored by Sec14p is °C uptake measurements the of the as as Cho that Cho from the medium is not by the of Sfh2p and Sfh4p in Sec14p-proficient cells. The turnover at 37 °C of cells was to the sec14ts strain. cells a intracellular GPCho, with the of Cho to the Spo14p of the by Sfh4p to the absence of Sec14p. 37 °C and are sec14ts is that of Sfh2p and Sfh4p the cells from the absence of Sec14p through a that not restore the of PC turnover to the Sec14p-proficient cell. The analyses performed in and cells in a sec14Δ background revealed a profound alteration of PC metabolism triggered by the absence of Sec14p: Nte1p unresponsiveness, Spo14p activation, and deregulation of activity. In cells by the of Sfh2p and Sfh4p new PC metabolism are to Sec14p the PC from the CDP-Cho pathway by of the at the as as increased PC deacylation by Nte1p. the and cells of Sec14p not the through this pathway at the by as is observed in Sec14p-proficient cells. In CDP-Cho PC is degraded by Nte1p Sec14p is a turnover of PC by Spo14p is as in these cells the intracellular Cho content is in Sec14p-proficient cells. The metabolic that the PC turnover by Spo14p to the observed in intracellular Cho choline uptake measurements performed in and cells for the in cells revealed that choline uptake was that of and cells. with this measurements of the activity of the Cho was reduced in cells but not in cells. Sfh2p- and Sfh4p-overexpressing cells Cho medium 10 mm Cho. The that and cells the of the CDP-Cho pathway by controlling the rate of through limiting the amount of Cho available for this and by actively excreting Cho from the cell. was observed that Spo14p results in Cho but the this is V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). is that Spo14p by or associated with at the membrane actively Cho of the as are the metabolic and choline in this an Cho by Spo14p activity are the where with the intracellular of PC by Spo14p results in an in intracellular Cho in the the CDP-Cho pathway for PC PC turnover by Spo14p results in Cho as a to Cho for the CDP-Cho pathway and through this of Cho from the is not by our that of Cho by yeast cells in 10 mm an Cho to the intracellular of Cho. We observed that cells Cho, and this was was cells also reduced Cho uptake in the absence of this that PC synthesis by actively decreased Cho uptake in to its increasing turnover of of PC homeostasis a between PC synthesis and In this we that Cho by Spo14p activity can be used for PC synthesis by the CDP-Cho PC turnover by Spo14p results in Cho from the as a to Cho to the CDP-Cho pathway in PC metabolic are used to processes with PC turnover as a positive regulator of V. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, M. Bankaitis V.A. PubMed Scopus Google and PC synthesis through the CDP-Cho pathway of this pathway (4Cleves A.E. McGee T.P. Whitters E.A. Champion K.M. Aitken J.R. Dowhan W. Goebl M. Bankaitis V.A. Cell. 1991; 64: 789-800Abstract Full Text PDF PubMed Scopus (286) Google Scholar, McMaster C.R. Biol. Cell. 2001; PubMed Scopus Google Scholar). Sec14p was to PC homeostasis actively by the for PC synthesis H.B. McGee T.P. McMaster C.R. Bankaitis V.A. PubMed Scopus Google and the new PC metabolic control features we ascribe to Sfh2p and we also describe a second role for Sec14p in mediating PC homeostasis with Sec14p as a positive regulator of Nte1p-mediated PC

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