Defining the importance of phosphatidylserine synthase-1 (PSS1) - Unexpected viability of PSS1-deficient mice
Defining the importance of phosphatidylserine synthase-1 (PSS1) - Unexpected viability of PSS1-deficient mice
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DOI：
10.1074/jbc.m800714200
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发表时间：
2008-05-09
影响因子：
4.8
通讯作者：
Vance, Jean E.
中科院分区：
文献类型：
--
作者：
Arikketh, Devi;Nelson, Randy;Vance, Jean E.
磷脂酰丝氨酸（PS）是哺乳动物细胞中数量较少但生理上重要的磷脂。PS由两种不同的碱基交换酶合成，PS合成酶-1（PSS 1）和PS合成酶-2（PSS 2），它们由不同的基因编码。PSS 1将丝氨酸交换为磷脂酰胆碱的胆碱，而PSS 2将磷脂酰乙醇胺的乙醇胺交换为丝氨酸。我们先前产生了缺乏PSS 2的小鼠（Bergo，M. O.，佳维诺，B。J.，斯滕贝尔根，R.，Sturbois，B.，Parlow，A. F.、Sanan，D.一、Skarnes，W. C.的方法，万斯，J.E.，和Young，S. G.（2002）J.Biol.Chem.277，47701-47708），并发现PSS 2不是小鼠生存力所必需的。我们现在已经产生了PSS 1缺陷小鼠。鉴于缺乏PSS 1的中国仓鼠卵巢细胞的存活率明显受损，我们惊讶地发现PSS 1缺陷小鼠是可行的，可生育的，并且具有正常的寿命。Pss 1（-/-）小鼠组织中的总丝氨酸交换活性（由PSS 1和PSS 2贡献）减少了85%，但除肝脏外，PS含量没有改变。尽管推测PS在神经系统中的重要性，但PSS 1缺陷神经元的轴突延伸速率是正常的。Pss 1（-/-）小鼠和Pss 2（-/-）小鼠的杂交产生了具有三个破坏的Pss等位基因的小鼠，但没有双敲除小鼠。在Pss 1（-/-）/Pss 2（-/-）和Pss 1（-/-）/Pss 2（-/-）小鼠中，丝氨酸交换活性降低65- 91%，PS和磷脂酰乙醇胺的组织含量也降低。我们的结论是：（i）消除PSS 1或PSS 2，但不是两者，是与小鼠的生存能力，（ii）小鼠可以耐受低至10%的正常总丝氨酸交换活性，和（iii）小鼠生存与PS和磷脂酰乙醇胺含量显着降低。
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, serine-exchange 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.