O-mannosylation is required for degradation of the endoplasmic reticulum-associated degradation substrate Gas1*p via the ubiquitin/proteasome pathway in Saccharomyces cerevisiae
O-mannosylation is required for degradation of the endoplasmic reticulum-associated degradation substrate Gas1*p via the ubiquitin/proteasome pathway in Saccharomyces cerevisiae
复制标题
DOI：
10.1093/jb/mvm249
复制
发表时间：
2008-04-01
影响因子：
2.7
通讯作者：
Jigami, Yoshifumi
中科院分区：
文献类型：
--
作者：
Hirayama, Hiroto;Fujita, Morihisa;Jigami, Yoshifumi
在酿酒酵母中，由蛋白质 O-甘露糖基转移酶执行的蛋白质 O-甘露糖基化对于多种生物过程以及赋予错误折叠蛋白质溶解度至关重要。为了确定 O-甘露糖基化是否在错误折叠蛋白的内质网相关降解 (ERAD) 中发挥重要作用，我们使用了错误折叠蛋白模型 Gas1*p。由蛋白质O-甘露糖基转移酶转移的Gas1*p的O-甘露糖含量高于Gas1p。 Pmt1p 和 Pmt2p 均不会将 O-甘露糖转移至正确折叠的 Gas1p，但参与了 Gas1*p 的 O-甘露糖基化。此外，在 pmt1 Delta pmt2 Delta 双突变体背景下，Gas1*p 的降解从主要依赖于蛋白酶体的途径转变为依赖于液泡蛋白酶的途径。该过程在某种程度上依赖于 VPS30 复合体 II 的高尔基体到内体的分选功能。总的来说，我们的数据表明，O-甘露糖基化在 Gas1*p 通过 ERAD 途径的蛋白酶体依赖性降解中发挥着重要作用，当 O-甘露糖基化不足时，Gas1*p 在液泡中降解。因此，我们认为 Pmt1p 和 Pmt2p 的 O-甘露糖基化可能是通过蛋白酶体依赖性 ERAD 途径靶向某些错误折叠蛋白进行降解的关键步骤。
In Saccharomyces cerevisiae, protein O-mannosylation, which is executed by protein O-mannosyltransferases, is essential for a variety of biological processes as well as for conferring solubility to misfolded proteins. To determine if O-mannosylation plays an essential role in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins, we used a model misfolded protein, Gas1*p. The O-mannose content of Gas1*p, which is transferred by protein O-mannosyltransferases, was higher than that of Gas1p. Both Pmt1p and Pmt2p, which do not transfer O-mannose to correctly folded Gas1p, participated in the O-mannosylation of Gas1*p. Furthermore, in a pmt1 Delta pmt2 Delta double-mutant background, degradation of Gas1*p is altered from a primarily proteasome dependent to a vacuolar protease-dependent pathway. This process is in a manner dependent on a Golgi-to-endosome sorting function of the VPS30 complex II. Collectively, our data suggest that O-mannosylation plays an important role for proteasome-dependent degradation of Gas1*p via the ERAD pathway and when O-mannosylation is insufficient, Gas1*p is degraded in the vacuole. Thus, we propose that O-mannosylation by Pmt1p and Pmt2p might be a key step in the targeting of some misfolded proteins for degradation via the proteasome-dependent ERAD pathway.