Golgi-mediated vacuolar sorting of the endoplasmic reticulum chaperone BiP may play an active role in quality control within the secretory pathway
Golgi-mediated vacuolar sorting of the endoplasmic reticulum chaperone BiP may play an active role in quality control within the secretory pathway
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DOI：
10.1105/tpc.105.036665
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发表时间：
2006-01-01
期刊：
影响因子：
11.6
通讯作者：
Denecke, J
中科院分区：
文献类型：
--
作者：
Pimpl, P;Taylor, JP;Denecke, J
内质网（ER）中的质量控制防止不正确或不完全折叠的蛋白质到达其最终目的地，并靶向永久错误折叠的蛋白质进行降解。这种蛋白质对ER伴侣BiP具有高亲和力，并且最终通过从ER腔逆行易位回到细胞溶质而降解。这种ER相关蛋白降解（ERAD）目前被认为是主要的处置途径，但越来越多的证据表明空泡在质量控制中的作用。我们表明，在烟草（Nicotiana tabacum）中，BiP以渥曼青霉素敏感的方式被运输到液泡中，并且它可能在第二种处置途径中发挥积极作用。BiP的ER输出通过COPII依赖性转运发生到高尔基体，在高尔基体中它与其他HDEL受体配体竞争。当HDEL介导的检索从高尔基体失败，BiP被运送到裂解液泡通过多泡体，这代表了植物prevacuolar室。我们还表明，一个子集的BiP-配体复合物是注定的液泡和不同的那些可能会被处置通过ERAD途径。除ERAD外，双极性处理还可以发挥作用，以最大限度地提高分泌途径中的质量控制效率。
Quality control in the endoplasmic reticulum ( ER) prevents the arrival of incorrectly or incompletely folded proteins at their final destinations and targets permanently misfolded proteins for degradation. Such proteins have a high affinity for the ER chaperone BiP and are finally degraded via retrograde translocation from the ER lumen back to the cytosol. This ER-associated protein degradation (ERAD) is currently thought to constitute the main disposal route, but there is growing evidence for a vacuolar role in quality control. We show that BiP is transported to the vacuole in a wortmannin-sensitive manner in tobacco (Nicotiana tabacum) and that it could play an active role in this second disposal route. ER export of BiP occurs via COPII-dependent transport to the Golgi apparatus, where it competes with other HDEL receptor ligands. When HDEL-mediated retrieval from the Golgi fails, BiP is transported to the lytic vacuole via multivesicular bodies, which represent the plant prevacuolar compartment. We also demonstrate that a subset of BiP-ligand complexes is destined to the vacuole and differs from those likely to be disposed of via the ERAD pathway. Vacuolar disposal could act in addition to ERAD to maximize the efficiency of quality control in the secretory pathway.