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Specific presynaptic functions require distinct Drosophila Cav2 splice isoforms.

Christopher Bell1, Lukas Kilo2, Daniel Gottschalk1

  • 1Johannes Gutenberg University Mainz, Institute of Developmental Biology and Neurobiology, Biocenter 1, Mainz, Germany.

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Summary

In Drosophila, alternative splicing of the Cacophony (cac) calcium channel fine-tunes presynaptic function. Specific splicing events regulate channel localization and impact synaptic transmission and plasticity.

Keywords:
Cav2D. melanogasteralternative splicingcacophonyneurosciencesynapsesynaptic function

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Vertebrate synapses utilize diverse Cav2 channel subtypes to regulate presynaptic function.
  • Invertebrates typically possess a single Cav2 gene, suggesting alternative mechanisms for functional diversification.
  • The Drosophila Cav2 homolog, cacophony (cac), is crucial for synaptic vesicle release at active zones (AZs).

Purpose of the Study:

  • To investigate how alternative splicing of the Drosophila cac gene enhances functional diversity.
  • To determine the roles of two specific mutually exclusive exon pairs in cac channel function.
  • To elucidate the impact of alternative splicing on presynaptic calcium channel localization and synaptic transmission.

Main Methods:

  • Analysis of alternative splicing events in the Drosophila cac gene.
  • Electrophysiological recordings at the Drosophila larval neuromuscular junction.
  • Immunolocalization studies to determine channel localization at presynaptic active zones.

Main Results:

  • Alternative splicing in the voltage sensor domain alters channel activation voltage; only the higher-activation voltage isoform localizes to AZs and is essential for normal synapse function.
  • Alternative splicing in the Caβ/Gβγ binding loop affects AZ channel number, release probability, and presynaptic homeostatic plasticity.
  • Reduced channel number due to splicing impacts short-term plasticity, which can be rescued by adjusting external calcium concentrations.

Conclusions:

  • Alternative splicing of the single Drosophila cac gene provides a versatile mechanism to regulate distinct aspects of presynaptic function.
  • Splicing-dependent localization and expression levels of cac channels are critical for synaptic transmission and plasticity.
  • This study highlights alternative splicing as a key strategy for diversifying ion channel function in invertebrates.