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Updated: Jun 6, 2026
Using Drosophila Larval Neuromuscular Junction and Muscle Cells to Visualize Microtubule Network
Published on: October 20, 2023
The Drosophila miR-310 cluster negatively regulates synaptic strength at the neuromuscular junction
Kazuya Tsurudome1, Karen Tsang, Edward H Liao
1Department of Physiology, McGill University, Montréal, QC H3G 1Y6, Canada.
Abstract:
Emerging data implicate microRNAs (miRNAs) in the regulation of synaptic structure and function, but we know little about their role in the regulation of neurotransmission in presynaptic neurons. Here, we demonstrate that the miR-310-313 cluster is required for normal synaptic transmission at the Drosophila larval neuromuscular junction. Loss of miR-310-313 cluster leads to a significant enhancement of neurotransmitter release, which can be rescued with temporally restricted expression of mir-310-313 in larval presynaptic neurons. Kinesin family member, Khc-73 is a functional target for miR-310-313 as its expression is increased in mir-310-313 mutants and reducing it restores normal synaptic function. Cluster mutants show an increase in the active zone protein Bruchpilot accompanied by an increase in electron dense T bars. Finally, we show that repression of Khc-73 by miR-310-313 cluster influences the establishment of normal synaptic homeostasis. Our findings establish a role for miRNAs in the regulation of neurotransmitter release.
Insights
The miR-310-313 cluster is crucial for normal neurotransmission. Its absence enhances neurotransmitter release by upregulating Khc-73, impacting synaptic homeostasis.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNAs (miRNAs) are increasingly recognized for their roles in synaptic plasticity and function.
- However, their specific involvement in regulating neurotransmission within presynaptic neurons remains largely unexplored.
Purpose of the Study:
- To investigate the role of the miR-310-313 cluster in regulating neurotransmission at the Drosophila larval neuromuscular junction.
- To identify functional targets of the miR-310-313 cluster involved in synaptic transmission.
Main Methods:
- Utilized Drosophila larval neuromuscular junction as a model system.
- Employed genetic manipulation to study the effects of miR-310-313 cluster loss and restoration.
- Analyzed neurotransmitter release, protein expression (Khc-73, Bruchpilot), and ultrastructural changes (T bars).
Main Results:
- Loss of the miR-310-313 cluster significantly enhances neurotransmitter release.
- Kinesin family member Khc-73 was identified as a functional target; its increased expression in mutants was rescued by reducing Khc-73 levels, restoring normal synaptic function.
- Mutants exhibited increased active zone protein Bruchpilot and electron-dense T bars.
- miR-310-313 cluster repression of Khc-73 influences synaptic homeostasis establishment.
Conclusions:
- The miR-310-313 cluster is essential for normal synaptic transmission by regulating presynaptic neurotransmitter release.
- Khc-73 is a key target mediating the effects of this miRNA cluster on synaptic function and homeostasis.
- This study establishes a novel role for miRNAs in the precise regulation of neurotransmitter release and synaptic integrity.
