GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory
Open accessPublished version of a preprint
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Zhang, Y., Chen, K., Sloan, S. A., Bennett, M. L., Scholze, A. R., O'Keeffe, S., Phatnani, H. P., Guarnieri, P., Caneda, C., Ruderisch, N., et al. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.1860-14.2014 · Cited by 4,875 · cited 2× · see citing works
“According to the brain RNA-seq database, full-length TMEM87A (isoform 1) is highly expressed in both, neurons and astrocytes 24,25 .”
MethodHighly accurate protein structure prediction for the human proteome
Tunyasuvunakool, K., Adler, J., Wu, Z., Green, T., Zielinski, M., Žídek, A., Bridgland, A., Cowie, A., Meyer, C., Laydon, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03828-1 · Cited by 3,025 · cited 2× · see citing works
“However, the results of structure prediction with AlphaFold2 32 indicated that the ELD structure of hTMEM87A and hTMEM87B were highly similar (Supplementary Fig.”
MethodCryo-EM structures of the TMEM16A calcium-activated chloride channel
Dang, S., Feng, S., Tien, J., Peters, C. J., Bulkley, D., Lolicato, M., Zhao, J., Zuberbühler, K., Ye, W., Qi, L., et al. (2017) · Nature · doi:10.1038/nature25024 · Cited by 333 · see citing works
Structural basis for channel conduction in the pump-like channelrhodopsin ChRmine
Kishi, K. E., Kim, Y. S., Fukuda, M., Inoue, M., Kusakizako, T., Wang, P. Y., Ramakrishnan, C., Byrne, E. F. X., Thadhani, E., Paggi, J. M., et al. (2022) · Cell · doi:10.1016/j.cell.2022.01.007 · Cited by 149 · see citing works
Flagged first, then by citations
- Authors
- Kang, H., Han, A.-R., Zhang, A., Jeong, H., Koh, W., Lee, J. M., Lee, H., Jo, H. Y., Maria-Solano, M. A., Bhalla, M., Kwon, J., Roh, W. S., Yang, J., An, H. J., Choi, S., Kim, H. M., & Lee, C. J.
- Affiliations
- Institute for Basic Science (KR)
- Ewha Womans University (KR)
- Chungnam National University (KR)
- ORCID
- Venue
- Nature Communications
- Published
- 2024-07-11
- Volume
- 15
- Issue
- 1
- Pages
- 5830-5830
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC11239671
- OpenAlex
- W4400543074
- Cited by
- 18
- References
- 5
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 2
- FWCI
- 4.03
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- 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
- Institute for Basic Science (IBS-R001-D2, IBS-R001-Y1, IBS-R030-C1)
- National Research Foundation of Korea (NRF-2022M3E5F3080873, NRF- 2021H1D3A2A02038434, NRF-2021H1D3A2A02081370NRF-2018R1A5A2025286,)
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
