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Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis.

Overview

Authors: Luca Lo Piccolo1, Ranchana Yeewa1, Pitiporn Noisagul1, Arnaud Monteil2,3, Vorasuk Shotelersuk4,5, Salinee Jantrapirom6,7
ORCID iDs: Luca Lo Piccolo
  1. Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  2. Institut de Génomique Fonctionnelle, Université de Montpellier, CNRS, INSERM, Montpellier, France
  3. Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
  4. Center of Excellence for Medical Genomics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand
  5. Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society, Bangkok, Thailand
  6. Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
  7. Drosophila Centre for Human Diseases and Drug Discovery (DHD), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
Institutions: Chiang Mai University (Thailand); Centre National de la Recherche Scientifique (France); Siriraj Hospital (Thailand); Inserm (France); Université de Montpellier (France); Mahidol University (Thailand); Institut de Génomique Fonctionnelle (France); Thai Red Cross Society (Thailand); Chulalongkorn University (Thailand); King Chulalongkorn Memorial Hospital (Thailand)
Journal: iScience, volume 29, issue 6, article 115855
Dates: received 13 September 2025; accepted 20 April 2026; published online 22 April 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1016/j.isci.2026.115855 · PMID 42109848 · PMCID PMC13156693 · OpenAlex W4414114722
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.09.06.674642
Status: code on request
Categories: cellular / molecular (subfield)
Methods: Spectral & time-frequency, Statistics, Evoked potentials, fMRI & imaging
Keywords: Epigenetics, Molecular neuroscience
Topic: Neurobiology and Insect Physiology Research (Cellular and Molecular Neuroscience, Neuroscience), according to OpenAlex
Funding: Chiang Mai University (FF68/207569); Faculty of Medicine, Chiang Mai University (FACMED 139/2567); National Research Council of Thailand (N42A670768); Health Systems Research Institute
Citations: cited by 2 papers (Europe PMC); 51 references in the paper
Research resources: Anti-rabbit IgG (H + L)-HRP Conjugate RRID:AB_11125142, GFP RRID:AB_221569, RRID:AB_2534073, RRID:AB_2534079, Anti-mouse IgG (H + L)-HRP Conjugate RRID:AB_2921252, Tyrosine hydroxylase (TH) RRID:AB_390204, Actin RRID:AB_528068, Fasciclin-2 (FasII) RRID:AB_528235, R softaware v4.1 RRID:SCR_001905, GraphPad software v.9 RRID:SCR_002798, GSEA software v4.3.2 RRID:SCR_003199

Abstract

YEATS2 is a chromatin-associated factor that regulates dopaminergic (DAergic) synaptic integrity, although its mechanism of action remains unclear. Here, we profiled head transcriptomic changes following neuron-specific YEATS2 knockdown in Drosophila. This analysis revealed coordinated downregulation of metabolic genes alongside upregulation of G protein-coupled receptor (GPCR) signaling components. YEATS2 loss led to elevated intracellular calcium, indicating calcium overload in the nervous system, and was associated with seizure-like activity, locomotor deficits, and loss of DAergic neurons, while sparing glutamatergic neurons and mushroom bodies. Genetic and pharmacological inhibition of store-operated calcium entry (SOCE) via the Orai channel, as well as blockade of ryanodine receptors, improved stress-induced phenotypes, restored calcium balance, and preserved DAergic neuron integrity. Together, these findings identify ER-centered calcium dysregulation as a key downstream consequence of YEATS2 loss and define a YEATS2-dependent epigenetic-calcium axis that links chromatin regulation to neuronal excitability and selective dopaminergic vulnerability.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

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Data

Datasets cited

Data and code availability

RNA-seq data have been deposited in GEO under accession number GSE:GSE307078 (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE307078), and the associated BioProject has been deposited under accession number PRJNA1314219 (https://ncbi.nlm.nih.gov/sra?term=PRJNA1314219). These data are publicly available as of the date of publication.

Original western blot images are included in the supplemental information. Microscopy data reported in this paper will be shared by the lead contact upon request.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY-NC), 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, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 2 keywords, 4 funders, 49 references, 11 RRIDs.

Cite

This paper

Lo Piccolo, L., Yeewa, R., Noisagul, P., Monteil, A., Shotelersuk, V., & Jantrapirom, S. (2026). Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis. iScience, 29(6), 115855. https://doi.org/10.1016/j.isci.2026.115855

BibTeX

@article{lopiccolo2026dopaminergic,
author = {Lo Piccolo, Luca and Yeewa, Ranchana and Noisagul, Pitiporn and Monteil, Arnaud and Shotelersuk, Vorasuk and Jantrapirom, Salinee},
title = {{Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis}},
journal = {iScience},
year = {2026},
month = apr,
volume = {29},
number = {6},
pages = {115855},
publisher = {Elsevier},
issn = {2589-0042},
doi = {10.1016/j.isci.2026.115855},
url = {https://doi.org/10.1016/j.isci.2026.115855},
pmid = {42109848},
pmcid = {PMC13156693}
}

RIS

TY - JOUR
AU - Lo Piccolo, Luca
AU - Yeewa, Ranchana
AU - Noisagul, Pitiporn
AU - Monteil, Arnaud
AU - Shotelersuk, Vorasuk
AU - Jantrapirom, Salinee
TI - Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis
T2 - iScience
J2 - iScience
PY - 2026
DA - 2026/04/22
VL - 29
IS - 6
SP - 115855
SN - 2589-0042
PB - Elsevier
DO - 10.1016/j.isci.2026.115855
UR - https://doi.org/10.1016/j.isci.2026.115855
LA - en
ER -

CSL-JSON

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