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The conserved microRNA miR-34 regulates synaptogenesis via coordination of distinct mechanisms in presynaptic and postsynaptic cells

McNeill, Elizabeth M., Warinner, Chloe, Alkins, Stephen, Taylor, Alicia, Heggeness, Hansine, DeLuca, Todd F., Fulga, Tudor A., Wall, Dennis P., Griffith, Leslie C., Van Vactor, David·2020·Nature Communications
DOI 10.1038/s41467-020-14761-8PMC PMC7046720
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Abstract

Micro(mi)RNA-based post-transcriptional regulatory mechanisms have been broadly implicated in the assembly and modulation of synaptic connections required to shape neural circuits, however, relatively few specific miRNAs have been identified that control synapse formation. Using a conditional transgenic toolkit for competitive inhibition of miRNA function in Drosophila, we performed an unbiased screen for novel regulators of synapse morphogenesis at the larval neuromuscular junction (NMJ). From a set of ten new validated regulators of NMJ growth, we discovered that miR-34 mutants display synaptic phenotypes and cell type-specific functions suggesting distinct downstream mechanisms in the presynaptic and postsynaptic compartments. A search for conserved downstream targets for miR-34 identified the junctional receptor CNTNAP4/Neurexin-IV (Nrx-IV) and the membrane cytoskeletal effector Adducin/Hu-li tai shao (Hts) as proteins whose synaptic expression is restricted by miR-34. Manipulation of miR-34, Nrx-IV or Hts-M function in motor neurons or muscle supports a model where presynaptic miR-34 inhibits Nrx-IV to influence active zone formation, whereas, postsynaptic miR-34 inhibits Hts to regulate the initiation of bouton formation from presynaptic terminals.

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  • At the Drosophila neuromuscular junction, miR-34 controls synaptogenesis by regulating distinct pre- and postsynaptic genes.

    “as well as from the Drosophila neuromuscular junction, where miR‐34 controls synaptogenesis by regulating distinct pre‐ and postsynaptic genes (McNeill et al., 2020).”

    From MicroRNA‐138‐5p suppresses excitatory synaptic strength at the cerebellar input layer (2025) · cites this paper as McNeill et al., 2020

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Metadata

Authors
McNeill, E. M., Warinner, C., Alkins, S., Taylor, A., Heggeness, H., DeLuca, T. F., Fulga, T. A., Wall, D. P., Griffith, L. C., & Van Vactor, D.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-02-27
Volume
11
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-020-14761-8
PMC
PMC7046720
Cited by
51
References
7
Language
en
Licence
Funders
U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NS090994, NS069695)

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