Bat3 promotes the membrane integration of tail-anchored proteins
Bat3 promotes the membrane integration of tail-anchored proteins
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DOI：
10.1242/jcs.066738
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发表时间：
2010-07-01
影响因子：
4
通讯作者：
High, Stephen
中科院分区：
文献类型：
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作者：
Leznicki, Pawel;Clancy, Anne;High, Stephen
尾锚定蛋白在内质网（ER）的膜整合是翻译后的，不同的尾锚定蛋白利用不同的胞质因子。例如，哺乳动物TRC40在将尾锚定蛋白递送至ER期间具有明确的作用。尽管已知其酿酒酵母等同物Get3与至少四种其他组分Get1、Get2、Get4和Get5（Mdy2）协同作用，但在尾锚定蛋白生物发生期间其他哺乳动物蛋白的作用尚不清楚。为此，我们分析了Sec61 β（TRC40的明确底物）的胞质结合伴侣，并将Bat3鉴定为以前未知的相互作用伴侣。Bat3的耗尽抑制Sec61 β的膜整合，但不抑制第二种不依赖于TRC40的尾锚定蛋白细胞色素b5的膜整合。因此，Bat3使用TRC40途径影响尾锚定蛋白的体外膜整合。当在缺乏用于尾锚定蛋白生物合成的功能性GET途径的酿酒酵母中表达时，Bat3与所得的非靶向链的胞质池缔合并将其转移到细胞核。这种蝙蝠3介导的错误定位是不依赖于Sgt2，最近确定的酵母GET途径的组成部分，我们建议，蝙蝠3要么调节TRC40途径在高等真核生物或提供一个新合成的尾锚定蛋白的替代命运。
The membrane integration of tail-anchored proteins at the endoplasmic reticulum (ER) is post-translational, with different tail-anchored proteins exploiting distinct cytosolic factors. For example, mammalian TRC40 has a well-defined role during delivery of tail-anchored proteins to the ER. Although its Saccharomyces cerevisiae equivalent, Get3, is known to function in concert with at least four other components, Get1, Get2, Get4 and Get5 (Mdy2), the role of additional mammalian proteins during tail-anchored protein biogenesis is unclear. To this end, we analysed the cytosolic binding partners of Sec61 beta, a well-defined substrate of TRC40, and identified Bat3 as a previously unknown interacting partner. Depletion of Bat3 inhibits the membrane integration of Sec61 beta, but not of a second, TRC40-independent, tail-anchored protein, cytochrome b5. Thus, Bat3 influences the in vitro membrane integration of tail-anchored proteins using the TRC40 pathway. When expressed in Saccharomyces cerevisiae lacking a functional GET pathway for tail-anchored protein biogenesis, Bat3 associates with the resulting cytosolic pool of non-targeted chains and diverts it to the nucleus. This Bat3-mediated mislocalisation is not dependent upon Sgt2, a recently identified component of the yeast GET pathway, and we propose that Bat3 either modulates the TRC40 pathway in higher eukaryotes or provides an alternative fate for newly synthesised tail-anchored proteins.