Oku Masaya, Tanakura Soichiro, Uemura Aya, Sohda Miwa, Misumi Yoshio, Taniguchi Mai, Wakabayashi Sadao, Yoshida Hiderou
Department of Biophysics, Graduate School of Science, Kyoto University, Japan.
Cell Struct Funct. 2011;36(1):1-12. doi: 10.1247/csf.10014. Epub 2010 Dec 8.
When increased production of secretory proteins overwhelms the capacity of the endoplasmic reticulum (ER) and the Golgi apparatus, eukaryotic cells expand their capacity to sustain secretory function. The capacity of the ER is enhanced by the mechanism called the ER stress response, but the mechanism regulating Golgi capacity (the Golgi stress response) has remained unclear. Here, we found that transcription of Golgi-related genes, including glycosylation enzymes as well as factors involved in post-Golgi vesicular transport and maintenance of Golgi structure, was upregulated upon treatment with monensin, an ionophore that disrupts the function of acidic organelles, including the Golgi apparatus and lysosomes by neutralizing their lumen. This transcriptional induction was found to be commonly regulated by a novel cis-acting element called the Golgi apparatus stress response element (GASE), whose consensus sequence is ACGTGgc. When the function of the Golgi apparatus was specifically disturbed by overexpression of GCP60, a Golgi-localized protein that binds to giantin, transcription from GASE was significantly induced. These results suggest that mammalian cells have the Golgi stress response, and that GASE regulates transcriptional induction involved in the Golgi stress response.
当分泌蛋白产量增加，超出内质网（ER）和高尔基体的处理能力时，真核细胞会扩展自身能力以维持分泌功能。内质网的能力通过一种名为内质网应激反应的机制得以增强，但调节高尔基体能力的机制（高尔基体应激反应）仍不明确。在此，我们发现，在用莫能菌素处理后，与高尔基体相关的基因转录上调，这些基因包括糖基化酶、高尔基体后囊泡运输及高尔基体结构维持相关因子。莫能菌素是一种离子载体，通过中和酸性细胞器（包括高尔基体和溶酶体）的内腔来破坏其功能。这种转录诱导作用被发现通常受一种名为高尔基体应激反应元件（GASE）的新型顺式作用元件调控，其共有序列为ACGTGgc。当通过过表达GCP60（一种与巨蛋白结合的高尔基体定位蛋白）特异性干扰高尔基体功能时，来自GASE的转录会被显著诱导。这些结果表明，哺乳动物细胞存在高尔基体应激反应，且GASE调节高尔基体应激反应中涉及的转录诱导。
