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Updated: May 12, 2026

Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons
Published on: September 9, 2020
Dopaminergic neurons are vulnerable to dysregulation of YEATS2-dependent calcium homeostasis
Luca Lo Piccolo1, Ranchana Yeewa1, Pitiporn Noisagul1
1Center of Multidisciplinary Technology for Advanced Medicine (CMUTEAM), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
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.
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