Aihua Zhang (이화여자대학교)

한빛사논문

조회149

Aihua ZhangAihua Zhang

이화여자대학교

Nat. Commun., Jul 11 2024, 15 (1) | https://doi.org/10.1038/s41467-024-49297-8 GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory

Hyunji Kang^1,2,7, Ah-reum Han^3,7, Aihua Zhang^4,7, Heejin Jeong⁵, Wuhyun Koh¹, Jung Moo Lee¹, Hayeon Lee¹, Hee Young Jo⁵, Miguel A. Maria-Solano⁴, Mridula Bhalla¹, Jea Kwon¹, Woo Suk Roh¹, Jimin Yang³, Hyun Joo An⁵, Sun Choi⁴, Ho Min Kim^3,6 & C. Justin Lee^1,2

¹Center for Cognition and Sociality, Life Science Cluster, Institute for Basic Science (IBS), 55 Expo-ro, Yuseong-gu, Daejeon 34126, Republic of Korea.

²IBS School, University of Science and Technology (UST), 217 Gajeong-ro, Yuseong-gu, Daejeon 34113, Republic of Korea.

³Center for Biomolecular and Cellular Structure, Life Science Cluster, Institute for Basic Science (IBS), 55 Expo-ro, Yuseong-gu, Daejeon 34126, Republic of Korea.

⁴Global AI Drug Discovery Center, College of Pharmacy and Graduate School of Pharmaceutical Science, Ewha Womans University, Seoul 03760, Republic of Korea.

⁵Graduate School of Analytical Science and Technology, Chungnam National University, Daejeon 34134, Korea.

⁶Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

⁷These authors contributed equally: Hyunji Kang, Ah-reum Han, Aihua Zhang.

Corresponding authors

Correspondence to Sun Choi, Ho Min Kim or C. Justin Lee.

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.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-12)
연구진국내 연구진
분야 생명과학 > 세포생물학

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