14-3-3ζ escorts CCTα for calcium-activated nuclear import in lung epithelia
14-3-3ζ escorts CCTα for calcium-activated nuclear import in lung epithelia
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DOI：
10.1096/fj.09-136044
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发表时间：
2010-04-01
期刊：
影响因子：
4.8
通讯作者：
Mallampalli, Rama K.
中科院分区：
文献类型：
--
作者：
Agassandian, Marianna;Chen, Bill B.;Mallampalli, Rama K.
动物生物膜的完整性对于保持正常细胞功能和活力至关重要。磷脂酰胆碱是一种不可或缺的膜成分，其生物合成需要 CCT α 酶。核膜网络的扩展需要 CCT α 的核表达，但 CCT α 核输入的机制尚不清楚。在此，我们发现在上皮细胞中，细胞外 Ca2+ 触发 CCT α 细胞质-核易位。 CCT α 核输入与 14-3-3 zeta（蛋白质运输的关键调节因子）的结合有关。 14-3-3 zeta 既足够又是 CCT α 核导入所必需的。 14-3-3 zeta 结合沟内的螺旋 G 与 CCT α 羧基末端磷酸丝氨酸基序（残基 328-343）内的推定分子特征相互作用。在铜绿假单胞菌感染模型中，上皮内 Ca2+ 浓度增加，14-3-3 zeta 在保护磷脂酰胆碱合成和细胞活力方面发挥着至关重要的作用。因此，14-3-3 zeta 响应钙信号控制 CCT α 核输入，从而调节哺乳动物磷脂合成。 Agassandian, M.、Chen, B. B.、Schuster, C. C.、Houtman, J. C. D.、Mallampalli, R. K. 14-3-3 zeta 护送 CCT α 进行肺上皮细胞中的钙激活核输入。 FASEB J. 24, 1271-1283 (2010)。 www.fasebj.org
Integrity of animal biomembranes is critical to preserve normal cellular functions and viability. Phosphatidylcholine, an indispensible membrane component, requires the enzyme CCT alpha for its biosynthesis. Nuclear expression of CCT alpha is needed for expansion of the nuclear membrane network, but mechanisms for CCT alpha nuclear import are unknown. Herein, we show that in epithelia, extracellular Ca2+ triggers CCT alpha cytoplasmic-nuclear translocation. CCT alpha nuclear import was associated with binding to 14-3-3 zeta, a key regulator of protein trafficking. 14-3-3 zeta was both sufficient and required for CCT alpha nuclear import. Helix G within the 14-3-3 zeta binding groove interacts with a putative molecular signature within the CCT alpha carboxyl-terminal phosphoserine motif (residues 328-343). 14-3-3 zeta was critically involved in preserving phosphatidylcholine synthesis and cell viability in a model of Pseudomonas aeruginosa infection where Ca2+ concentrations increase within epithelia. Thus, 14-3-3 zeta controls CCT alpha nuclear import in response to calcium signals, thereby regulating mammalian phospholipid synthesis. Agassandian, M., Chen, B. B., Schuster, C. C., Houtman, J. C. D., Mallampalli, R. K. 14-3-3 zeta escorts CCT alpha for calcium-activated nuclear import in lung epithelia. FASEB J. 24, 1271-1283 (2010). www.fasebj.org