Toxin pores endocytosed during plasma membrane repair traffic into the lumen of MVBs for degradation.
Toxin pores endocytosed during plasma membrane repair traffic into the lumen of MVBs for degradation.
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在质膜修复流量中，内吞毒素孔进入MVB的流水中以降解。
DOI：
10.1111/j.1600-0854.2011.01323.x
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Andrews NW
中科院分区：
文献类型：
--
作者：
Corrotte M;Fernandes MC;Tam C;Andrews NW
细胞透化的细菌孔形成毒素链球菌溶血素O（SLO）重新密封其质膜在Ca 2+依赖性的方式。再密封涉及溶酶体的Ca 2+依赖性胞吐、酸性鞘磷脂酶的释放和携带跨膜孔进入细胞的内体的快速形成。然而，携带毒素的内吞囊泡的细胞内命运仍然未知。在这里，我们表明，SLO孔从质膜内吞作用被分类到溶酶体的内腔，在那里它们被降解。SLO透化的细胞含有增加数量的总内体，其大小逐渐增加，同时从具有平坦网格蛋白包衣的内体过渡到大的多泡体（MVB）。在允许内吞作用和质膜修复的条件下，SLO被迅速泛素化并逐渐降解，这一过程对溶酶体水解抑制剂敏感，但对蛋白酶体不敏感。由SLO透化诱导的内体在正常条件下变得越来越酸化并促进SLO降解，但在Vps 24表达沉默的细胞中不是这样，Vps 24是一种ESCRT-III复合物组分，用于将管腔内囊泡释放到MVB中。因此，细胞通过泛素化/ESCRT依赖性分选将SLO跨膜孔处理到晚期内体/溶酶体的内腔中。
Cells permeabilized by the bacterial pore-forming toxin streptolysin O (SLO) reseal their plasma membrane in a Ca2+-dependent manner. Resealing involves Ca2+-dependent exocytosis of lysosomes, release of acid sphingomyelinase and rapid formation of endosomes that carry the transmembrane pores into the cell. The intracellular fate of the toxin-carrying endocytic vesicles, however, is still unknown. Here, we show that SLO pores removed from the plasma membrane by endocytosis are sorted into the lumen of lysosomes, where they are degraded. SLO-permeabilized cells contain elevated numbers of total endosomes, which increase gradually in size while transitioning from endosomes with flat clathrin coats to large multivesicular bodies (MVBs). Under conditions that allow endocytosis and plasma membrane repair, SLO is rapidly ubiquitinated and gradually degraded, in a process sensitive to inhibitors of lysosomal hydrolysis but not of proteasomes. The endosomes induced by SLO permeabilization become increasingly acidified and promote SLO degradation under normal conditions, but not in cells silenced for expression of Vps24, an ESCRT-III complex component required for the release of intraluminal vesicles into MVBs. Thus, cells dispose of SLO transmembrane pores by ubiquitination/ESCRT-dependent sorting into the lumen of late endosomes/lysosomes.
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DOI：
10.1038/nrm2937
发表时间：
2010-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
30.3
作者：
Los FC;Kao CY;Smitham J;McDonald KL;Ha C;Peixoto CA;Aroian RV
通讯作者：
Aroian RV
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：
12.4
作者：
Hurley JH;Stenmark H
通讯作者：
Stenmark H
影响因子：
3.5
作者：
Husmann, Matthias;Beckmann, Erik;Bhakdi, Sucharit
通讯作者：
Bhakdi, Sucharit