PreprintCited by 18Cellular transport and secretionIon channel regulation and functionCalcium signaling and nucleotide metabolism

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GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory

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Lee, C. Justin, Kang, Hyunji, Han, Ah-reum, Zhang, Aihua, Jeong, Heejin, Koh, Wuhyun, Lee, Jung Moo, Lee, Hayeon, Jo, Heeyoung, Maria-Solano, Miguel A, Bhalla, Mridula, Roh, Woo Suk, Jang, Hyun Jun, Yang, Jimin, Lee, Boyoung, Choi, Sun, An, Hyun Joo, Kim, Ho Min, Kwon, Jea·2024·Nature Communications

Preprint — published as 10.1038/s41467-024-49297-8 · Paper page

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 found that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gained 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 novel molecular target for Golgi-related diseases and cognitive impairment.

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Metadata

Authors
Lee, C. J., Kang, H., Han, A.-R., Zhang, A., Jeong, H., Koh, W., Lee, J. M., Lee, H., Jo, H., Maria-Solano, M. A., Bhalla, M., Roh, W. S., Jang, H. J., Yang, J., Lee, B., Choi, S., An, H. J., Kim, H. M., & Kwon, J.
Affiliations
  • Institute for Basic Science (KR)
  • Ewha Womans University (KR)
  • Chungnam National University (KR)
  • Ewha Womans University
  • Institute for Basic Science (IBS)
  • Chungnam National University
  • KAIST
Venue
Nature Communications
Published
2024-03-20
Volume
15
Issue
1
Pages
5830-5830
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4400543074
Cited by
18
References
1
Citations by year
2026: 10 · 2025: 6 · 2024: 2
FWCI
4.03
Type
journal article
Language
en
Open access
Locations
  • Nature Communications (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Research Foundation (2018R1A5A2025286)
  • Korea Institute of Science and Technology
  • Korea Institute of Science and Technology Information
  • National Research Foundation of Korea (NRF2021H1D3A2A02038434, - 2018R1A5A2025286, NRF-2018R1A5A2025286, NRF-2021H1D3A2A02081370, NRF-2022M3E5F3080873, NRF-2022M3E5F3080873, NRF- 2021H1D3A2A02038434, NRF-2021H1D3A2A02081370NRF-2018R1A5A2025286,, NRF-2021H1D3A2A02081370NRF-2018R1A5A2025286, 2022M3E5F3080873)
  • Institute for Basic Science (IBS-R001, IBS-R030-C1, IBS-R001-Y1, IBSR001-D2)
  • Ministry of Science and ICT, South Korea (NRF 2021H1D3A2A02038434, 2018R1A5A2025286, NRF-2018R1A5A2025286, IBS-R001-D2)
  • Medical Research Council
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
Golgi apparatus, hippocampal-dependent memory, spatial memory, astrocytes, neurons, Golgi fragmentation, protein glycosylation, Alzheimer's disease, cognitive impairment, ion channel structure
MeSH terms
Animals, Astrocytes, Glycosylation, Golgi Apparatus, Hippocampus, Humans, Hydrogen-Ion Concentration, Ion Channels, Male, Membrane Proteins, Memory, Mice, Inbred C57BL, Neurons, Mice, Knockout, Cryoelectron Microscopy, Mice, HEK293 Cells, Cognitive Dysfunction, Spatial Memory

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