The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplamic sequences.
The Golgi localization of GOLPH2 (GP73/GOLM1) is determined by the transmembrane and cytoplamic sequences.
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DOI：
10.1371/journal.pone.0028207
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Peng T
中科院分区：
文献类型：
--
作者：
Hu L;Li L;Xie H;Gu Y;Peng T
高尔基体磷蛋白2（Golgi phosphoprotein 2，GOLPH 2）是一种在肝脏疾病中上调的高尔基体II型膜蛋白。考虑到GOLPH 2通过内体运输并可以分泌到循环中，它是肝脏疾病的有希望的血清标志物。GOLPH 2的结构及其不同蛋白结构域的功能尚不清楚。在目前的研究中，我们调查了高尔基体定位使用一组GOLPH 2截断突变体的结构决定因素。GOLPH 2的高尔基体定位不受蛋白质C-末端部分缺失的影响。一种截短的突变体，含有定位于高尔基体的N-末端部分（胞质尾和跨膜结构域（TMD））。N-末端的序列缺失分析表明，在胞质N-末端尾带正电荷的残基的TMD足以支持高尔基体定位。我们还表明，内源性和分泌GOLPH 2存在作为二硫键键二聚体，卷曲螺旋结构域是足够的二聚化。这些结构知识对于理解GOLPH 2在肝脏疾病中的致病作用以及开发基于GOLPH 2的肝细胞癌诊断方法是重要的。
Golgi phosphoprotein 2 (GOLPH2) is a resident Golgi type-II membrane protein upregulated in liver disease. Given that GOLPH2 traffics through endosomes and can be secreted into the circulation, it is a promising serum marker for liver diseases. The structure of GOLPH2 and the functions of its different protein domains are not known. In the current study, we investigated the structural determinants for Golgi localization using a panel of GOLPH2 truncation mutants. The Golgi localization of GOLPH2 was not affected by the deletion of the C-terminal part of the protein. A truncated mutant containing the N-terminal portion (the cytoplasmic tail and transmembrane domain (TMD)) localized to the Golgi. Sequential deletion analysis of the N-terminal indicated that the TMD with a positively charged residue in the cytoplasmic N-terminal tail were sufficient to support Golgi localization. We also showed that both endogenous and secreted GOLPH2 exist as a disulfide-bonded dimer, and the coiled-coil domain was sufficient for dimerization. This structural knowledge is important for the understanding the pathogenic role of GOLPH2 in liver diseases, and the development of GOLPH2-based hepatocellular cancer diagnostic methods.
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影响因子：
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作者：
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