Perforin rapidly induces plasma membrane phospholipid flip-flop.
Perforin rapidly induces plasma membrane phospholipid flip-flop.
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穿孔蛋白迅速诱导质膜磷脂触发器。
DOI：
10.1371/journal.pone.0024286
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Froelich CJ
中科院分区：
文献类型：
--
作者：
Metkar SS;Wang B;Catalan E;Anderluh G;Gilbert RJ;Pardo J;Froelich CJ
细胞毒颗粒的分泌途径是宿主防御所必需的。该途径基本上是细胞内蛋白递送的一种形式，其中来自细胞毒性淋巴细胞的颗粒蛋白酶（颗粒酶）被认为通过孔形成蛋白穿孔素（PFN）在靶细胞的质膜中产生的桶形板条孔扩散，并介导凋亡以及另外的生物学效应。虽然最近的电子显微镜和结构分析表明，重组PFN寡聚化，形成含有20个单体（20 nm）的孔时，施加到脂质体膜，这些孔没有观察到碘化丙啶摄取靶细胞。相反，促进颗粒酶介导的细胞凋亡的人PFN浓度与通过膜联蛋白-V和Lactadherin测量的出乎意料地有利于磷脂酰丝氨酸翻转的孔结构相关。减少靶点中PFN介导的Ca内流的努力并没有降低Annexin-V的反应性。抗原特异性小鼠CD 8细胞在靶细胞中启动类似的快速翻转。一种增加质膜曲率以及靶细胞胆固醇消耗的脂质增强了触发器。Annexin-V染色与颗粒酶B（Gzm B）处理后的细胞凋亡高度相关。我们提出的结构，PFN低聚物形成的膜双层可能包括弧以前观察到的电子显微镜和这些不寻常的结构代表了质膜脂质和PFN低聚物，可能作为一个灵活的网关GzmB跨跨双层易位到靶细胞的胞质小叶的不完全混合物。
The cytotoxic cell granule secretory pathway is essential for host defense. This pathway is fundamentally a form of intracellular protein delivery where granule proteases (granzymes) from cytotoxic lymphocytes are thought to diffuse through barrel stave pores generated in the plasma membrane of the target cell by the pore forming protein perforin (PFN) and mediate apoptotic as well as additional biological effects. While recent electron microscopy and structural analyses indicate that recombinant PFN oligomerizes to form pores containing 20 monomers (20 nm) when applied to liposomal membranes, these pores are not observed by propidium iodide uptake in target cells. Instead, concentrations of human PFN that encourage granzyme-mediated apoptosis are associated with pore structures that unexpectedly favor phosphatidylserine flip-flop measured by Annexin-V and Lactadherin. Efforts that reduce PFN mediated Ca influx in targets did not reduce Annexin-V reactivity. Antigen specific mouse CD8 cells initiate a similar rapid flip-flop in target cells. A lipid that augments plasma membrane curvature as well as cholesterol depletion in target cells enhance flip-flop. Annexin-V staining highly correlated with apoptosis after Granzyme B (GzmB) treatment. We propose the structures that PFN oligomers form in the membrane bilayer may include arcs previously observed by electron microscopy and that these unusual structures represent an incomplete mixture of plasma membrane lipid and PFN oligomers that may act as a flexible gateway for GzmB to translocate across the bilayer to the cytosolic leaflet of target cells.
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DOI：
10.1083/jcb.200210158
发表时间：
2003-03-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Metkar SS;Wang B;Ebbs ML;Kim JH;Lee YJ;Raja SM;Froelich CJ
通讯作者：
Froelich CJ
DOI：
10.1083/jcb.200708010
发表时间：
2008-03-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Idone V;Tam C;Goss JW;Toomre D;Pypaert M;Andrews NW
通讯作者：
Andrews NW
影响因子：
32.4
作者：
Keefe, D;Shi, LF;Lieberman, J
通讯作者：
Lieberman, J
影响因子：
4.4
作者：
Hirt, UA;Gantner, F;Leist, M
通讯作者：
Leist, M
影响因子：
32.4
作者：
Metkar, SS;Wang, BK;Froelich, CJ
通讯作者：
Froelich, CJ