Externalization of phosphatidylserine during apoptosis does not specifically require either isoform of phosphatidylserine synthase

Grandmaison, Paul A.; Nanowski, Terry S.; Vance, Jean E.

doi:10.1016/j.bbalip.2003.11.004

Cited by 14 publications

(9 citation statements)

References 69 publications

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“…Some of the PS exposed during apoptosis was reported to be newly synthesized [28]. Nevertheless, in cells in which total PS biosynthetic activity was reduced by 95% [29], apoptosis progressed normally and PS exposure on the cell exterior during apoptosis was not compromised [30]. In addition, the exposure of PS on the surface of red blood cells serves as a signal for eryptosis (the clearance of red blood cells from the circulation by phagocytic cells) [31,32].…”

Section: Transbilayer Movement Of Ps In the Plasma Membranementioning

confidence: 97%

Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells

Vance

Tasseva

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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482

431

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Section: Transbilayer Movement Of Ps In the Plasma Membranementioning

confidence: 97%

Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells

Vance

Tasseva

2013

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

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482

431

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“…In the absence of PS supplementation the double mutant cells did not survive, and the content of PS and PE was 80 and 49% lower, respectively, than in wild-type CHO cells. Despite only ϳ5% of normal serine-exchange activity, PS externalization occurs normally on the cell surface of these CHO double mutants during apoptosis (35).…”

Section: Discussionmentioning

confidence: 99%

Defining the Importance of Phosphatidylserine Synthase-1 (PSS1)

Devi

Nelson

Vance

2008

Journal of Biological Chemistry

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Phosphatidylserine (PS) is a quantitatively minor, but physiologically important, phospholipid in mammalian cells. PS is synthesized by two distinct base-exchange enzymes, PS synthase-1 (PSS1) and PS synthase-2 (PSS2), that are encoded by different genes. PSS1 exchanges serine for choline of phosphatidylcholine, whereas PSS2 exchanges ethanolamine of phosphatidylethanolamine for serine. We previously generated mice lacking PSS2 (Bergo, M. O., Gavino, B. J., Steenbergen, R., Sturbois, B., Parlow, A. F., Sanan, D. A., Skarnes, W. C., Vance, J. E., and Young, S. G. (2002) J. Biol. Chem. 277, 47701-47708) and found that PSS2 is not required for mouse viability. We have now generated PSS1-deficient mice. In light of the markedly impaired survival of Chinese hamster ovary cells lacking PSS1 we were surprised that PSS1-deficient mice were viable, fertile, and had a normal life span. Total serine-exchange activity (contributed by PSS1 and PSS2) in tissues of Pss1 ؊/؊ mice was reduced by up to 85%, but except in liver, the PS content was unaltered. Despite the presumed importance of PS in the nervous system, the rate of axonal extension of PSS1-deficient neurons was normal. Intercrosses of Pss1 ؊/؊ mice and Pss2 ؊/؊ mice yielded mice with three disrupted Pss alleles but no double knockout mice. In Pss1 /Pss2؉/؊ and Pss1 ؉/؊ /Pss2؊/؊ mice, serineexchange activity was reduced by 65-91%, and the tissue content of PS and phosphatidylethanolamine was also decreased. We conclude that (i) elimination of either PSS1 or PSS2, but not both, is compatible with mouse viability, (ii) mice can tolerate as little as 10% of normal total serine-exchange activity, and (iii) mice survive with significantly reduced PS and phosphatidylethanolamine content. Phosphatidylserine (PS)2 is a quantitatively minor phospholipid comprising 3-10% of total phospholipids of mammalian cell membranes. PS is synthesized by two distinct base-exchange enzymes, phosphatidylserine synthase-1 (PSS1) and phosphatidylserine synthase-2 (PSS2) (for a review, see Ref. 1). Each PS synthase is encoded by a different gene, but the enzymes share 32% amino acid identity (2). These two synthases are integral membrane proteins located primarily in mitochondria-associated membranes (MAM) (3). MAM comprise a specialized domain of the endoplasmic reticulum and are thought to mediate the import of PS into mitochondria via transient contact between MAM and mitochondrial outer membranes (4, 5). The PS synthases catalyze base-exchange reactions in which serine is exchanged for the polar head group of either phosphatidylcholine (PC) (PSS1 exchanges choline for serine) or phosphatidylethanolamine (PE) (PSS2 exchanges ethanolamine for serine).Mutant Chinese hamster ovary (CHO) cells lacking PSS1 require supplementation with either ethanolamine (20 M) or PS (10 -50 M) for survival (6, 7). In the absence of added ethanolamine, the mutant cells grow for two doublings, exhibit rounded morphology, and subsequently die, whereas the addition of ethanolamine supports growth (6). Normal growt...

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“…The biosynthetic origin of the PS that is externalized during apoptosis was investigated in studies in CHO mutant cells that lacked either PS synthase-1 [36,174] or PS synthase-2 [45], or CHO cells that were deficient in both isoforms of PS synthase [45]. Apoptosis was induced by incubation of the cells with staurosporine [203]. In the cells lacking either PS synthase-1 or PS synthase-2, the serine-exchange activity was reduced while the PS content of the cells was unaltered.…”

Section: Biological Consequences Of Ps Exposure On the Outside Of Cellsmentioning

confidence: 99%

Metabolism and functions of phosphatidylserine

Vance

Steenbergen

2005

Progress in Lipid Research

441

402

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Externalization of phosphatidylserine during apoptosis does not specifically require either isoform of phosphatidylserine synthase

Cited by 14 publications

References 69 publications

Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells

Formation and function of phosphatidylserine and phosphatidylethanolamine in mammalian cells

Defining the Importance of Phosphatidylserine Synthase-1 (PSS1)

Metabolism and functions of phosphatidylserine

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