November 9, 20250 citationsOpen Access

Regulation of miR-219 and its target RalGPS dictates acute synaptic plasticity at the Drosophila neuromuscular junction

KAKumar Aavula HHHansine Heggeness TYTakakazu Yokokura

Key Points

Synaptic plasticity involves Ral signaling, with miR-219 playing a critical role in regulating this process.
Post-transcriptional regulatory mechanism impacts presynaptic morphogenesis in response to neural activity at the Drosophila neuromuscular junction.
Drosophila model provides insights into how structural synaptic plasticity occurs through miRNA-mediated controls.
Adaptive responses in synapses are dictated by the interplay between miRNAs like miR-219 and their targets, such as RalGPS.

Abstract

RNA regulatory mechanisms mediate adaptive responses requiring rapid gene expression changes. Examining microRNA (miRNA)-mediated control of structural synaptic plasticity, we identified miR-219 and six other conserved miRNAs regulating activity-induced morphogenesis at Drosophila glutamatergic synapses. Among miRNA targets downregulated by acute stimulation, the Ral-activating factor RalGPS is necessary for presynaptic morphogenesis and sufficient to block plasticity. Stimulation elevates miR-219 loading into Argonaute complexes without altering mature miR-219 levels, revealing a post-transcriptional regulatory mechanism. We conclude that activity-induced miRNA loading modulates Ral signaling via RalGPS to enable presynaptic remodeling and growth, establishing a novel link between neuronal activity and synaptic structural plasticity.

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