The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium.
The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium.
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LRR和环域蛋白LRSAM1是一种E3连接酶，对于细胞内沙门氏菌的泛素依赖性自噬至关重要。
DOI：
10.1016/j.chom.2012.10.019
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发表时间：
2012-12-13
影响因子：
30.3
通讯作者：
Xavier RJ
中科院分区：
文献类型：
--
作者：
Huett A;Heath RJ;Begun J;Sassi SO;Baxt LA;Vyas JM;Goldberg MB;Xavier RJ
几种病原菌在细胞内的空泡内复制。逃逸到细胞质中的细菌被自噬途径捕获，并以溶酶体降解为目标，代表着对宿主细胞质的细菌利用的防御。鼠伤寒沙门氏菌的自噬捕获主要是通过在胞液细菌周围产生多泛素信号、结合接头蛋白和招募自噬机制来实现的。然而，介导细菌靶标选择和泛素化的成分仍然不清楚。我们确定LRSAM1是负责抗沙门氏菌自噬相关泛素化的E3连接酶。LRSAM1定位于几种细胞内的细菌病原体，并产生与细菌相关的泛素信号；这些功能分别需要LRSAM1的S富含亮氨酸的重复结构域和环域。使用LRSAM1缺陷个体的细胞，我们证实LRSAM1是与细胞内细菌相关的泛素化所必需的，但对于聚集蛋白的泛素化是必不可少的。因此，LRSAM1是一种细菌识别蛋白和泛素连接酶，保护细胞质免受侵袭性病原体的侵袭。
Several species of pathogenic bacteria replicate within an intracellular vacuolar niche. Bacteria that escape into the cytosol are captured by the autophagic pathway and targeted for lysosomal degradation, representing a defense against bacterial exploitation of the host cytosol. Autophagic capture of Salmonella Typhimurium occurs predominantly via generation of a polyubiquitin signal around cytosolic bacteria, binding of adaptor proteins, and recruitment of autophagic machinery. However, the components mediating bacterial target selection and ubiquitination remain obscure. We identify LRSAM1 as the E3 ligase responsible for anti-Salmonella autophagy-associated ubiquitination. LRSAM1 localizes to several intracellular bacterial pathogens and generates the bacteria-associated ubiquitin signal; these functions require LRSAM1’s leucine-rich repeat and RING domains, respectively. Using cells from LRSAM1-deficient individuals, we confirm that LRSAM1 is required for ubiquitination associated with intracellular bacteria but dispensable for ubiquitination of aggregated proteins. LRSAM1 is therefore a bacterial recognition protein and ubiquitin ligase that defends the cytoplasm from invasive pathogens.
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影响因子：
6.1
作者：
Tang, Bin;Seredenina, Tamara;Coppola, Giovanni;Kuhn, Alexandre;Geschwind, Daniel H.;Luthi-Carter, Ruth;Thomas, Elizabeth A.
通讯作者：
Thomas, Elizabeth A.
影响因子：
30.3
作者：
Shahnazari S;Yen WL;Birmingham CL;Shiu J;Namolovan A;Zheng YT;Nakayama K;Klionsky DJ;Brumell JH
通讯作者：
Brumell JH
DOI：
10.1073/pnas.1000093107
发表时间：
2011-03-15
影响因子：
11.1
作者：
Ng, Aylwin C. Y.;Eisenberg, Jason M.;Xavier, Ramnik J.
通讯作者：
Xavier, Ramnik J.
影响因子：
13.3
作者：
Cemma, Marija;Kim, Peter Kijun;Brumell, John Hunter
通讯作者：
Brumell, John Hunter
影响因子：
4.8
作者：
Smith, AC;Cirulis, JT;Brumell, JH
通讯作者：
Brumell, JH