Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis
Issued Date
2026-06-19
Resource Type
eISSN
25890042
Scopus ID
2-s2.0-105037713605
Journal Title
Iscience
Volume
29
Issue
6
Rights Holder(s)
SCOPUS
Bibliographic Citation
Iscience Vol.29 No.6 (2026)
Suggested Citation
Lo Piccolo L., Yeewa R., Noisagul P., Monteil A., Shotelersuk V., Jantrapirom S. Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis. Iscience Vol.29 No.6 (2026). doi:10.1016/j.isci.2026.115855 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/116683
Title
Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis
Corresponding Author(s)
Other Contributor(s)
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.