2024-07-24 韓国基礎科学研究院(IBS)
<関連情報>
- https://www.ibs.re.kr/cop/bbs/BBSMSTR_000000000738/selectBoardArticle.do
- https://www.nature.com/articles/s41467-024-49297-8
ゴルジ体に存在するユニークな電位依存性カチオンチャネルGolpHCat(TMEM87A)がゴルジ体pHの維持と海馬依存性記憶に寄与 GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory
Hyunji Kang,Ah-reum Han,Aihua Zhang,Heejin Jeong,Wuhyun Koh,Jung Moo Lee,Hayeon Lee,Hee Young Jo,Miguel A. Maria-Solano,Mridula Bhalla,Jea Kwon,Woo Suk Roh,Jimin Yang,Hyun Joo An,Sun Choi,Ho Min Kim & C. Justin Lee
Nature Communications Published:11 July 2024
DOI:https://doi.org/10.1038/s41467-024-49297-8
Abstract
Impaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer’s disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment.
