Regulated externalization of phosphatidylserine at the cell surface - Implications for apoptosis
Regulated externalization of phosphatidylserine at the cell surface - Implications for apoptosis
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DOI：
10.1074/jbc.m700202200
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发表时间：
2007-06-22
影响因子：
4.8
通讯作者：
Schroit, Alan J.
中科院分区：
文献类型：
--
作者：
Balasubramanian, Krishnakumar;Mirnikjoo, Banafsheh;Schroit, Alan J.
质膜磷脂酰丝氨酸(PS)不对称性的调节丢失是许多生物过程的关键。特别是，PS出现在细胞表面，这是细胞凋亡的标志，为死亡的细胞准备吞噬和清除吞噬细胞。虽然众所周知，PS外化是通过激活钙依赖的磷脂扰乱酶活性和失活氨基磷脂转位酶来调节的，但没有证据表明这些过程是由细胞凋亡调节机制触发和调节的。利用一个新的模型系统，我们证明PS的外化是可诱导的、可逆的，并且不依赖于细胞色素c的释放、caspase的激活和DNA的断裂。另有证据表明，质膜PS的外移需要胞内钙离子持续升高，同时氨基磷脂转位酶失活，并被钙通道阻滞剂抑制。
The regulated loss of plasma membrane phosphatidylserine ( PS) asymmetry is critical to many biological processes. In particular, the appearance of PS at the cell surface, a hallmark of apoptosis, prepares the dying cell for engulfment and elimination by phagocytes. While it is well established that PS externalization is regulated by activation of a calcium-dependent phospholipid scramblase activity in concert with inactivation of the aminophospholipid translocase, there is no evidence indicating that these processes are triggered and regulated by apoptotic regulatory mechanisms. Using a novel model system, we show that PS externalization is inducible, reversible, and independent of cytochrome c release, caspase activation, and DNA fragmentation. Additional evidence is presented indicating that the outward movement of plasma membrane PS requires sustained elevation in cytosolic Ca2+ in concert with inactivation of the aminophospholipid translocase and is inhibited by calcium channel blockers.