ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis.
The 3 matches · all tie a paragraph to a whole file, not to given lines: weak matches, whose lines are not tinted
- [1] § Results › ATP13A4 deficiency delays early postnatal neurodevelopment ↔ dev. milestones (fig. 6)/script_eyeopening.R, the whole file · a weak match · score 0.60 · postnatal day, eye open, KO pups, width, animals, model
- [2] § Results › ATP13A4 deficiency delays early postnatal neurodevelopment ↔ dev. milestones (fig. 6)/script_weight.R, the whole file · a weak match · score 0.52 · postnatal day, KO pups, weight, width, animals, model
- [3] § Results › ATP13A4 deficiency delays early postnatal neurodevelopment ↔ dev. milestones (fig. 6)/script_eyeopening.R, the whole file · a weak match · score 0.51 · eye opening, KO pups, postnatal, genotypes, animals, WT
Paper
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The authors' code
R · 73 lines · 1.6 KB · MIT · 2 matches
- # =========================
- # Eye opening analysis
- # =========================
- library(rstudioapi)
- dataFile <- selectDirectory(
- caption = "Select Directory",
- label = "Select",
- path = getActiveProject()
- )
- setwd(dataFile)
- getwd()
- list.files()
- library(readxl)
- library(dplyr)
- library(ordinal)
- library(ggplot2)
- list.files()
- df <- read_excel("eye_opening.xlsx")
- head(df)
- df <- df %>%
- filter(!is.na(animal), !is.na(genotype), !is.na(day), !is.na(score)) %>%
- mutate(
- animal = factor(animal),
- genotype = factor(genotype, levels = c("WT", "KO")),
- day = as.numeric(day),
- score = factor(score, levels = c(0, 1, 2), ordered = TRUE)
- )
- # Quick check
- str(df)
- table(df$genotype, df$score)
- model <- clmm(score ~ genotype * day + (1 | animal), data = df)
- summary(model)
- library(ggplot2)
- library(dplyr)
- plot_df <- df %>%
- mutate(score_num = as.numeric(as.character(score))) %>%
- group_by(genotype, day) %>%
- summarise(
- mean_score = mean(score_num),
- sd = sd(score_num),
- n = n(),
- se = sd / sqrt(n),
- .groups = "drop"
- )
- ggplot(plot_df, aes(x = day, y = mean_score, color = genotype, group = genotype)) +
- geom_line(linewidth = 1) +
- geom_point(size = 2) +
- geom_errorbar(aes(ymin = mean_score - se, ymax = mean_score + se), width = 0.2) +
- scale_y_continuous(breaks = c(0, 1, 2), limits = c(0, 2)) +
- labs(
- x = "Postnatal day",
- y = "Mean eye-opening score",
- title = "Eye opening in WT and KO pups"
- ) +
- theme_classic(base_size = 13)
- df %>%
- distinct(animal, genotype) %>%
- count(genotype)
script_eyeopening.R at commit bff244f, under MIT · at the source
Overview
16 affiliations
- Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium
- Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD USA
- Department of Cell Biology, Duke University Medical Center, Durham, NC USA
- Center for Pediatric Neurological Disease Research, St. Jude Children’s Research Hospital, Memphis, TN USA
- Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC USA
- Department of Neurobiology, Duke University Medical Center, Durham, NC USA
- Department of Neonatology, Children’s Mercy Hospital, Kansas City, MO USA
- Laboratory for Neurobiology and Gene Therapy, Department of Neurosciences, Leuven Brain Institute, KU Leuven, Leuven, Belgium
- Leuven Viral Vector Core, KU Leuven, Leuven, Belgium
- VIB-KU Leuven Center for Brain & Disease Research, Leuven, Belgium
- VIB-KU Leuven Center for Neuroscience, Electrophysiology Technology Unit, Leuven, Belgium
- Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany
- Department of Pediatric Neurology, Children’s Hospital Datteln, University Witten/Herdecke, Datteln, Germany
- Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL USA
- Department of Pathology, Northwestern University Feinberg School of Medicine, Chicago, IL USA
- Instituto de Investigação e Inovação em Saúde (i3S), University of Porto, Porto, Portugal
Abstract
Polyamines, such as spermidine, are essential regulators of brain development, yet how cells control their uptake and extracellular levels remains unclear. Here we show that ATP13A4, a transport protein enriched in glia and prominently expressed in astrocytes, governs brain polyamine balance. Using biochemical, cellular, and animal models, we find that ATP13A4 imports polyamines into cells and thereby limits their availability outside cells. Loss of ATP13A4 simplifies astrocyte morphology and increases the excitatory connections, or synapses, that astrocytes promote between neurons; adding spermidine reproduces these effects, identifying extracellular spermidine as a synapse-promoting signal. In mice lacking Atp13a4, brain polyamines are redistributed, with reduced levels in the cortex and accumulation in cerebrospinal fluid. This is accompanied by excess excitatory synapses, delayed early development, and mild, female-biased behavioral changes in adulthood. Rare ATP13A4 variants linked to neurodevelopmental disorders disrupt its function. Thus, astrocytic polyamine clearance via ATP13A4 tunes extracellular spermidine to shape synapse formation during development.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repositories
Its files are read in the Code ↔ Paper reader above, with 3 matches between paragraphs and lines of code.
Eroglu-Lab/In-Vitro-Sholl
7c358eca89be2501bab49419cc4fa0de9dc2c5f7, 3 February 2026Availability: 1 check, the latest on 26 September 2026: the link answers
- 26 September 2026: the link answers
3 files
- inVitro_sholl_analysis.r
, R, 104 lines - README.md, Text, 46 lines
- license.txt, License, 23 lines
emsm3eus-crypto/van-Veen-et-al.-2026
bff244f612510fdb138aca39b80b941595b56bdc, 11 June 2026Availability: 1 check, the latest on 26 September 2026: the link answers
- 26 September 2026: the link answers
11 files
- dev. milestones (fig. 6)/
script_eyeopening.R , R, 73 lines, 2 matches - dev. milestones (fig. 6)/
script_weight.R , R, 69 lines, 1 match - expression (supp. fig. 1-2)/
Bakken et al., 2021.R , R, 187 lines - expression (supp. fig. 1-2)/
Jorstad et al., 2023.R , R, 149 lines - expression (supp. fig. 1-2)/
Saunders et al., 2018.R , R, 133 lines - expression (supp. fig. 1-2)/
Schaum et al., 2018.R , R, 105 lines - expression (supp. fig. 1-2)/
Zhang et al., 2014.R , R, 76 lines - expression (supp. fig. 1-2)/
Zhang et al., 2016.R , R, 170 lines - sholl analysis (supp. fig. 9b)/
rescue_script.R , R, 65 lines - LICENSE, License, 21 lines
- README.md, Text, 146 lines
eroglu-lab/irala_2024_image_analysis
af4cba845a409d8f93c3f36678ec2b39703e15a7, 12 December 2023Availability: 1 check, the latest on 26 September 2026: the link answers
- 26 September 2026: the link answers
1 file
- README.md, Text, 2 lines
Eroglu-Lab
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
- 26 September 2026: the link answers (HTTP 200)
Zenodo 10779514
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
- 26 September 2026: the link answers (HTTP 200)
1 file
- README.md, Text, 2 lines
Zenodo 20490523
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
- 26 September 2026: the link answers (HTTP 200)
3 files
- inVitro_sholl_analysis.r
, R, 104 lines - README.md, Text, 46 lines
- license.txt, License, 23 lines
Zenodo 20137621
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
- 26 September 2026: the link answers (HTTP 200)
11 files
- dev. milestones (fig. 6)/
script_eyeopening.R , R, 73 lines - dev. milestones (fig. 6)/
script_weight.R , R, 69 lines - expression (supp. fig. 1-2)/
Bakken et al., 2021.R , R, 187 lines - expression (supp. fig. 1-2)/
Jorstad et al., 2023.R , R, 149 lines - expression (supp. fig. 1-2)/
Saunders et al., 2018.R , R, 133 lines - expression (supp. fig. 1-2)/
Schaum et al., 2018.R , R, 105 lines - expression (supp. fig. 1-2)/
Zhang et al., 2014.R , R, 76 lines - expression (supp. fig. 1-2)/
Zhang et al., 2016.R , R, 170 lines - sholl analysis (supp. fig. 9b)/
rescue_script.R , R, 65 lines - LICENSE, License, 21 lines
- README.md, Text, 146 lines
Code availability
All original code has been deposited on GitHub [https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
- 7 repositories of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
- 20 scripts, each with its path and the digest of its content;
- 3 matches between paragraphs of the paper and lines of the code (method lexical-v1);
- neither the text of the paper nor the code itself.
Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
Datasets cited
- ebi.ac.uk/
metabolights/ , at EMBL-EBI; found in “Data availability”mtbls14724 - geo:GSE73721, at NCBI GEO; found in “Data availability”
- pride:PXD063347, at PRIDE; found in “Data availability”
- zenodo:14717837, at Zenodo; found in “Data availability”
- zenodo:14719447, at Zenodo; found in “Data availability”
Data Availability Statement
The mass spectrometry proteomics data generated in this study have been deposited in the ProteomeXchange Consortium database via the PRIDE partner repository under accession code PXD063347 (https://
All original code has been deposited on GitHub [https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Resource and materials availability
Further information and requests for resources and reagents should be directed to and will be fulfilled by the lead contact, Sarah van Veen. This study did not generate new unique reagents. All experimental protocols are available via protocols.io [doi.org/
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 24 authors, 3 keywords, 14 MeSH terms, 2 funders, 146 references, 54 RRIDs.
Cite
This paper
van Veen, S., Meeus, E., Irala, D., Sakers, K., Liu, Z., Savage, J., Séjourné, G., Bindu, D. S., Ausloos, E., Grzesik, H. E., Dhondt, H., Schoonvliet, N., Van den Haute, C., Van Asselberghs, J., Montpeyó Garcia-Moreno, M., Wierda, K., Baekelandt, V., Platzer, K., Rostasy, K., . . . Vangheluwe, P. (2026). ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis. Nature communications, 17(1), 9395. https://
BibTeX
@article{vanveen2026atp1
author = {van Veen, Sarah and Meeus, Emily and Irala, Dolores and Sakers, Kristina and Liu, Zhaolin and Savage, Justin and Séjourné, Gabrielle and Bindu, Dhanesh Sivadasan and Ausloos, Elke and Grzesik, Hanna Elzbieta and Dhondt, Hanne and Schoonvliet, Nina and Van den Haute, Chris and Van Asselberghs, Joris and Montpeyó Garcia-Moreno, Marta and Wierda, Keimpe and Baekelandt, Veerle and Platzer, Konrad and Rostasy, Kevin and Yap, Kai Lee and Eggermont, Jan and Holt, Matthew G and Eroglu, Cagla and Vangheluwe, Peter},
title = {{ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis}},
journal = {Nature communications},
year = {2026},
month = aug,
volume = {17},
number = {1},
pages = {9395},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/
url = {https://
pmid = {42680725},
pmcid = {PMC13534584}
}
RIS
TY - JOUR
AU - van Veen, Sarah
AU - Meeus, Emily
AU - Irala, Dolores
AU - Sakers, Kristina
AU - Liu, Zhaolin
AU - Savage, Justin
AU - Séjourné, Gabrielle
AU - Bindu, Dhanesh Sivadasan
AU - Ausloos, Elke
AU - Grzesik, Hanna Elzbieta
AU - Dhondt, Hanne
AU - Schoonvliet, Nina
AU - Van den Haute, Chris
AU - Van Asselberghs, Joris
AU - Montpeyó Garcia-Moreno, Marta
AU - Wierda, Keimpe
AU - Baekelandt, Veerle
AU - Platzer, Konrad
AU - Rostasy, Kevin
AU - Yap, Kai Lee
AU - Eggermont, Jan
AU - Holt, Matthew G
AU - Eroglu, Cagla
AU - Vangheluwe, Peter
TI - ATP13A4 gates extracellular polyamine levels to control excitatory synaptogenesis
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/
VL - 17
IS - 1
SP - 9395
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/
UR - https://
LA - en
ER -
CSL-JSON
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