Manganese-induced trafficking and turnover of the cis-Golgi glycoprotein GPP130.
Manganese-induced trafficking and turnover of the cis-Golgi glycoprotein GPP130.
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DOI：
10.1091/mbc.e09-11-0985
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发表时间：
2010-04-01
影响因子：
3.3
通讯作者：
Linstedt AD
中科院分区：
文献类型：
--
作者：
Mukhopadhyay S;Bachert C;Smith DR;Linstedt AD
锰中毒是一种无法治愈的疾病。这项研究鉴定了一种对锰敏感的哺乳动物蛋白质。这些发现提供了生理条件下受调控分选的一个重要的、新颖的例子，特别是在管腔序列而不是细胞质序列赋予调控作用的情况下。锰是一种必需元素，接触过多也会产生神经毒性。然而，哺乳动物细胞中调节锰稳态的机制在很大程度上尚不清楚。由于细胞溶质 Mn 的增加会导致参与调节酵母细胞内 Mn 浓度的蛋白质定位发生快速变化，因此我们很感兴趣地发现，低浓度的细胞外 Mn 会诱导 130 kDa 的哺乳动物顺式高尔基体糖蛋白（GPP130）快速重新分布到多泡体。 GPP130 随后在溶酶体中被降解。 Mn 诱导的 GPP130 运输通过 Rab-7 依赖性途径从高尔基体发生，不需要通过质膜或早期内体。尽管 GPP130 的细胞质结构域对于其对 Mn 作出反应的能力来说是可有可无的，但其腔干结构域是必需的，并且它必须靶向顺式高尔基体才能发生 Mn 反应。 Remarkably, the stem domain was sufficient to confer Mn sensitivity to another cis-Golgi protein.我们的结果将 GPP130 的干结构域鉴定为哺乳动物细胞高尔基体腔中的新型 Mn 传感器。
Manganism is a disease with no cure. This study identifies a mammalian protein with manganese-sensitive trafficking. The findings provide an important, novel example of regulated sorting under physiological conditions particularly in that a lumenal, rather than cytoplasmic, sequence confers the regulation. Manganese is an essential element that is also neurotoxic at elevated exposure. However, mechanisms regulating Mn homeostasis in mammalian cells are largely unknown. Because increases in cytosolic Mn induce rapid changes in the localization of proteins involved in regulating intracellular Mn concentrations in yeast, we were intrigued to discover that low concentrations of extracellular Mn induced rapid redistribution of the mammalian cis-Golgi glycoprotein Golgi phosphoprotein of 130 kDa (GPP130) to multivesicular bodies. GPP130 was subsequently degraded in lysosomes. The Mn-induced trafficking of GPP130 occurred from the Golgi via a Rab-7–dependent pathway and did not require its transit through the plasma membrane or early endosomes. Although the cytoplasmic domain of GPP130 was dispensable for its ability to respond to Mn, its lumenal stem domain was required and it had to be targeted to the cis-Golgi for the Mn response to occur. Remarkably, the stem domain was sufficient to confer Mn sensitivity to another cis-Golgi protein. Our results identify the stem domain of GPP130 as a novel Mn sensor in the Golgi lumen of mammalian cells.
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突变动力蛋白的诱导特异性阻断内吞涂层囊泡的形成。
影响因子：
7.8
作者：
Damke, H;Baba, T;Warnock, D E;Schmid, S L
通讯作者：
Schmid, S L
影响因子：
4.5
作者：
Ihrke, G;Kyttälä, A;Luzio, JP
通讯作者：
Luzio, JP
DOI：
10.1196/annals.1306.018
发表时间：
2004-01-01
期刊：
REDOX-ACTIVE METALS IN NEUROLOGICAL DISORDERS
影响因子：
--
作者：
Olanow, CW
通讯作者：
Olanow, CW
影响因子：
7.5
作者：
Piper, Robert C.;Luzio, J. Paul
通讯作者：
Luzio, J. Paul
影响因子：
3.4
作者：
Crooks, Daniel R.;Welch, Nicholas;Smith, Donald R.
通讯作者：
Smith, Donald R.