Specific presynaptic functions require distinct Drosophila Cav2 splice isoforms

eLife, vol. 13

Abstract

At many vertebrate synapses, presynaptic functions are tuned by expression of different Ca v 2 channels. Most invertebrate genomes contain only one Ca v 2 gene. The Drosophila Ca v 2 homolog, cacophony (cac), induces synaptic vesicle release at presynaptic active zones (AZs). We hypothesize that Drosophila cac functional diversity is enhanced by two mutually exclusive exon pairs that are not conserved in vertebrates, one in the voltage sensor and one in the loop binding Ca β and G βγ subunits. We find that alternative splicing in the voltage sensor affects channel activation voltage. Only the isoform with the higher activation voltage localizes to AZs at the glutamatergic Drosophila larval neuromuscular junction and is imperative for normal synapse function. By contrast, alternative splicing at the other alternative exon pair tunes multiple aspects of presynaptic function. While expression of one exon yields normal transmission, expression of the other reduces channel number in the AZ and thus release probability. This also abolishes presynaptic homeostatic plasticity. Moreover, reduced channel number affects short-term plasticity, which is rescued by increasing the external calcium concentration to match release probability to control. In sum, in Drosophila alternative splicing provides a mechanism to regulate different aspects of presynaptic functions with only one Ca v 2 gene.

Authors 10

1. Lukas Kilo Aachen Lehrstuhl für Entwicklungsbiologie

   RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University, Lehrstuhl für Entwicklungsbiologie

2. Daniel Gottschalk

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

3. Jashar Arian

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

4. Lea Deneke

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

5. Hanna B. Kern

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

6. Christof Rickert

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

7. Oliver Kobler

   Leibniz Institute for Neurobiology

   Affiliation as printed

   Leibniz Institute for Neurobiology Magdeburg, Combinatorial NeuroImaging Core Facility

8. Martin Heine

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

9. Carsten Duch

   Johannes Gutenberg University Mainz

   Affiliation as printed

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

10. Stefanie Ryglewski

    Johannes Gutenberg University Mainz

    Affiliation as printed

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