Membrane repair triggered by cholesterol-dependent cytolysins is activated by mixed lineage kinases and MEK.
Membrane repair triggered by cholesterol-dependent cytolysins is activated by mixed lineage kinases and MEK.
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由胆固醇依赖性溶细胞素触发的膜修复由混合谱系激酶和MEK激活。
DOI：
10.1126/sciadv.abl6367
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发表时间：
2022-03-18
期刊：
影响因子：
13.6
通讯作者：
Keyel PA
中科院分区：
文献类型：
--
作者：
Ray S;Roth R;Keyel PA
在脓毒性心肌病或坏死性软组织感染期间，由细菌成孔毒素（如链球菌溶血素O或产气荚膜梭菌溶血素O）损伤的质膜的修复由几种蛋白质家族介导。然而，离子流入下游的这些蛋白质的激活知之甚少。在这里，我们证明了膜穿孔细菌胆固醇依赖性溶细胞素，钙离子流入激活混合谱系激酶3独立的蛋白激酶C或神经酰胺的产生。混合谱系激酶3解偶联丝裂原活化激酶激酶（MEK）和细胞外调节激酶（ERK）信号传导。MEK信号通过ERK非依赖性途径促进膜联蛋白A2膜的快速募集并增强微囊泡脱落。这一途径占70%的所有钙离子依赖性修复反应的链球菌溶血素O和产气荚膜梭菌溶素O，但只有50%的修复中间溶素。我们得出结论，混合谱系激酶信号通过MEK协调微泡脱落，这是对胆固醇依赖性溶细胞素的细胞生存的关键。与以前认为钙内流直接控制膜修复的观点相反，MEK招募膜联蛋白A2进行修复。
Repair of plasma membranes damaged by bacterial pore-forming toxins, such as streptolysin O or perfringolysin O, during septic cardiomyopathy or necrotizing soft tissue infections is mediated by several protein families. However, the activation of these proteins downstream of ion influx is poorly understood. Here, we demonstrate that following membrane perforation by bacterial cholesterol-dependent cytolysins, calcium influx activates mixed lineage kinase 3 independently of protein kinase C or ceramide generation. Mixed lineage kinase 3 uncouples mitogen-activated kinase kinase (MEK) and extracellular-regulated kinase (ERK) signaling. MEK signals via an ERK-independent pathway to promote rapid annexin A2 membrane recruitment and enhance microvesicle shedding. This pathway accounted for 70% of all calcium ion-dependent repair responses to streptolysin O and perfringolysin O, but only 50% of repair to intermedilysin. We conclude that mixed lineage kinase signaling via MEK coordinates microvesicle shedding, which is critical for cellular survival against cholesterol-dependent cytolysins. In contrast to previous views that calcium influx directly controls membrane repair, MEK recruits annexin A2 for repair.
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影响因子：
7.3
作者：
Goodfellow VS;Loweth CJ;Ravula SB;Wiemann T;Nguyen T;Xu Y;Todd DE;Sheppard D;Pollack S;Polesskaya O;Marker DF;Dewhurst S;Gelbard HA
通讯作者：
Gelbard HA
影响因子：
16.6
作者：
Boye TL;Maeda K;Pezeshkian W;Sønder SL;Haeger SC;Gerke V;Simonsen AC;Nylandsted J
通讯作者：
Nylandsted J
影响因子：
4.1
作者：
Genetos, Damian C.;Wong, Alice;Watari, Shinya;Yellowley, Clare E.
通讯作者：
Yellowley, Clare E.
DOI：
10.1016/j.bbamcr.2014.12.039
发表时间：
2015-10
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Dany M;Ogretmen B
通讯作者：
Ogretmen B
影响因子：
20.3
作者：
Canault, Matthias;Duerschmied, Daniel;Wagner, Denisa D.
通讯作者：
Wagner, Denisa D.