Regulation of miR-219 and its target RalGPS is essential for synaptic plasticity at the Drosophila neuromuscular junction.

Authors

Kumar Aavula, Hansine Heggeness, Takakazu Yokokura, Spyros Artavanis-Tsakonas, David Van Vactor

Published in

Proceedings of the National Academy of Sciences of the United States of America. Volume 123. Issue 44. Pages e2622609123. Nov 03, 2026. Epub Oct 27, 2026.

Abstract

RNA regulatory mechanisms mediate adaptive responses relying on rapid changes in gene expression. By examining microRNA (miRNA)-mediated control of structural synaptic plasticity, we find miR-219 and five other conserved miRNAs regulate 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 is sufficient to block plasticity. We find that RalGPS must be held within a narrow range of expression for structural remodeling to occur. Loss or excess of RalGPS both abolish activity-induced synapse growth. Without altering levels of mature miR-219, stimulation elevates miR-219 loading in Argonaute (Ago1)-containing complexes that mediate miRNA gene silencing. We also find that elevated Protein Kinase A activity suppresses miR-219 association with Ago1 and blocks activity-induced synaptic growth, suggesting that miRNA loading and unloading in neurons are both controlled by activity-dependent regulation of Ago1.

PMID:
42945240
Bibliographic data and abstract were imported from PubMed on 28 Oct 2026.

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