Deletion of yeast p24 genes activates the unfolded protein response
Deletion of yeast p24 genes activates the unfolded protein response
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DOI：
10.1091/mbc.12.4.957
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发表时间：
2001-04-01
影响因子：
3.3
通讯作者：
Barlowe, C
中科院分区：
文献类型：
--
作者：
Belden, WJ;Barlowe, C
缺乏功能性p24复合物的酵母细胞在内质网（ER）中积累分泌蛋白的子集，并增加含HDEL的ER居民（例如Kar 2 p/BiP）的细胞外分泌。我们报告说，p24功能的丧失导致未折叠蛋白反应（UPR）的激活，并导致KAR 2表达增加。HDEL受体（Erd 2 p）在p24缺失菌株中与野生型菌株一样具有功能性和运输性，但超过了修复途径的能力。激活UPR和提高KAR 2表达的其他条件也导致Kar 2 p的细胞外分泌。使用体外试验，重建出芽从ER，我们检测升高水平的Kar 2 p在ER衍生的囊泡从p24缺失菌株和野生型菌株与激活的UPR。在这些条件下，通过IRE 1缺失沉默UPR减少了Kar 2 p的分泌。我们认为UPR的激活在Kar 2 p的细胞外分泌中起着重要作用。
Yeast cells lacking a functional p24 complex accumulate a subset of secretory proteins in the endoplasmic reticulum (ER) and increase the extracellular secretion of HDEL-containing ER residents such as Kar2p/BiP. We report that a loss of p24 function causes activation of the unfolded protein response (UPR) and leads to increased KAR2 expression. The HDEL receptor (Erd2p) is functional and traffics in p24 deletion strains as in wild-type strains, however the capacity of the retrieval pathway is exceeded. Other conditions that activate the UPR and elevate KAR2 expression also lead to extracellular secretion of Kar2p. Using an in vitro assay that reconstitutes budding from the ER, we detect elevated levels of Kar2p in ER-derived vesicles from p24 deletion strains and from wild-type strains with an activated UPR. Silencing the UPR by IRE1 deletion diminished Kar2p secretion under these conditions. We suggest that activation of the UPR plays a major role in extracellular secretion of Kar2p.