Mice lacking WRB reveal differential biogenesis requirements of tail-anchored proteins in vivo.
Mice lacking WRB reveal differential biogenesis requirements of tail-anchored proteins in vivo.
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DOI：
10.1038/srep39464
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发表时间：
2016-12-21
影响因子：
4.6
通讯作者：
Vilardi F
中科院分区：
文献类型：
--
作者：
Rivera-Monroy J;Musiol L;Unthan-Fechner K;Farkas Á;Clancy A;Coy-Vergara J;Weill U;Gockel S;Lin SY;Corey DP;Kohl T;Ströbel P;Schuldiner M;Schwappach B;Vilardi F
尾部锚定（TA）蛋白在翻译后插入到膜中。TRC40途径通过WRB和CAML组成的受体将TA蛋白靶向到内质网。TRC40通路客户端已通过体外检测确定，然而，TRC40通路在体内的相关性仍然未知。我们在两个组织特异性WRB敲除小鼠模型中跟踪了TA蛋白的命运，发现它们在体外对TRC40途径的依赖并不能预测它们在体内对受体耗竭的反应。SNARE syntaxin 5 （Stx5）对TRC40通路的破坏极为敏感。筛选酵母TA蛋白与哺乳动物同源物，我们发现Stx5的特殊敏感性是保守的，可能是由于其细胞质结构域的聚集倾向。我们确定Stx5是一个自噬靶点，通过其他途径无效的膜靶向。我们的研究结果强调了TRC40通路与细胞蛋白酶抑制之间的密切关系。
Tail-anchored (TA) proteins are post-translationally inserted into membranes. The TRC40 pathway targets TA proteins to the endoplasmic reticulum via a receptor comprised of WRB and CAML. TRC40 pathway clients have been identified using in vitro assays, however, the relevance of the TRC40 pathway in vivo remains unknown. We followed the fate of TA proteins in two tissue-specific WRB knockout mouse models and found that their dependence on the TRC40 pathway in vitro did not predict their reaction to receptor depletion in vivo. The SNARE syntaxin 5 (Stx5) was extremely sensitive to disruption of the TRC40 pathway. Screening yeast TA proteins with mammalian homologues, we show that the particular sensitivity of Stx5 is conserved, possibly due to aggregation propensity of its cytoplasmic domain. We establish that Stx5 is an autophagy target that is inefficiently membrane-targeted by alternative pathways. Our results highlight an intimate relationship between the TRC40 pathway and cellular proteostasis.
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影响因子：
4.4
作者：
Daniele LL;Emran F;Lobo GP;Gaivin RJ;Perkins BD
通讯作者：
Perkins BD
影响因子：
64.5
作者：
Ast, Tslil;Cohen, Galit;Schuldiner, Maya
通讯作者：
Schuldiner, Maya
影响因子：
4
作者：
Favaloro, Vincenzo;Vilardi, Fabio;Dobberstein, Bernhard
通讯作者：
Dobberstein, Bernhard
DOI：
10.1073/pnas.1006036107
发表时间：
2010-07-06
影响因子：
11.1
作者：
Chartron, Justin W.;Suloway, Christian J. M.;Clemons, William M., Jr.
通讯作者：
Clemons, William M., Jr.
影响因子：
64.8
作者：
Khaminets, Aliaksandr;Heinrich, Theresa;Dikic, Ivan
通讯作者：
Dikic, Ivan