2022年9月3日
GPHR-mediated acidification of the Golgi lumen is essential for cholesterol biosynthesis in the brain.
FEBS letters
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- 巻
- 596
- 号
- 22
- 開始ページ
- 2873
- 終了ページ
- 2888
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1002/1873-3468.14491
The Golgi pH regulator (GPHR) is essential for maintaining the function and morphology of the Golgi apparatus through the regulation of luminal acidic pH. Abnormal morphology of the Golgi apparatus is associated with neurodegenerative diseases. Here, we found that knockout of GPHR in the mouse brain led to morphological changes in the Golgi apparatus and neurodegeneration, which included brain atrophy, neuronal cell death, and gliosis. Furthermore, in the GPHR knockout mouse brain, transcriptional activity of sterol regulatory element-binding protein 2 (SREBP2) decreased, resulting in a reduction in cholesterol levels. GPHR-deficient cells exhibited suppressed neurite outgrowth, which was recovered by exogenous expression of the active form of SREBP2. Our results show that GPHR-mediated luminal acidification of the Golgi apparatus maintains proper cholesterol levels and, thereby, neuronal morphology.
- ID情報
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- DOI : 10.1002/1873-3468.14491
- PubMed ID : 36056653