Inositol deacylation by Bst1p is required for the quality control of glycosylphosphatidylinositol-anchored proteins
Inositol deacylation by Bst1p is required for the quality control of glycosylphosphatidylinositol-anchored proteins
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DOI：
10.1091/mbc.e05-05-0443
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发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Jigami, Y
中科院分区：
文献类型：
--
作者：
Fujita, M;Yoko, T;Jigami, Y
错误折叠的蛋白质在内质网 (ER) 中被识别，运回细胞质，并被蛋白酶体降解。许多蛋白质通过内质网中的糖基磷脂酰肌醇 (GPI) 锚定进行加工和修饰，但 GPI 锚定蛋白质的质量控制机制仍不清楚。在这里，我们报告了错误折叠的 GPI 锚定蛋白的质量控制机制。我们构建了 β-1,3-葡聚糖基转移酶 Gas1p (Gas1*p) 的突变形式作为错误折叠 GPI 锚定蛋白的模型。 Gas1*p 用 GPI 锚进行修饰，但保留在 ER 中，并通过蛋白酶体快速降解。编码 GPI 肌醇脱酰酶的 BSTI 的破坏导致 Gas1*p 降解延迟。这种延迟是由于 Bst1p 的脱酰活性受到影响。参与 GPI 锚定蛋白浓度和 N-聚糖加工的基因的破坏对 Gas1*p 和可溶性错误折叠版本的羧肽酶 Y 的降解产生不同的影响。此外，Gas1*p 在体内与 Bst1p 和 BiP/Kar2p（一种分子伴侣）相关。我们的数据表明，GPI 肌醇脱酰化在 GPI 锚定蛋白的质量控制和 ER 相关降解中发挥着重要作用。
Misfolded proteins are recognized in the endoplasmic reticulum (ER), transported back to the cytosol, and degraded by the proteasome. A number of proteins are processed and modified by a glycosylphosphatidylinositol (GPI) anchor in the ER, but the quality control mechanisms of GPI-anchored proteins remain unclear. Here, we report on the quality control mechanism of misfolded GPI-anchored proteins. We have constructed a mutant form of the beta-1,3-glucanosyltransferase Gas1p (Gas1*p) as a model misfolded GPI-anchored protein. Gas1*p was modified with a GPI anchor but retained in the ER and was degraded rapidly via the proteasome. Disruption of BSTI, which encodes GPI inositol deacylase, caused a delay in the degradation of Gas1*p. This delay was because of an effect on the deacylation activity of Bst1p. Disruption of genes involved in GPI-anchored protein concentration and N-glycan processing caused different effects on the degradation of Gas1*p and a soluble misfolded version of carboxypeptidase Y. Furthermore, Gas1*p associated with both Bst1p and BiP/Kar2p, a molecular chaperone, in vivo. Our data suggest that GPI inositol deacylation plays important roles in the quality control and ER-associated degradation of GPI-anchored proteins.