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

ABSTRACT: YEATS2, a chromatin-associated factor, is essential for maintaining dopaminergic (DA) synaptic integrity, but the underlying mechanism remains unclear. Using Drosophila, we show that neuronal depletion of YEATS2 alters brain transcriptomes, downregulating metabolic genes and upregulating G protein–coupled receptors (GPCRs). This correlates with elevated intracellular calcium levels, leading to neurobehavioral deficits and selective DA neuron loss. Crucially, genetic or pharmacological inhibition of the store-operated calcium entry channel Orai restores calcium balance and rescues DA neuron survival. These findings reveal a YEATS2-dependent epigenetic–calcium axis critical for dopaminergic neuron vulnerability.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE307078 | GEO | 2026/04/11

REPOSITORIES: GEO

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

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