The role of alternative splicing of CaV2 channels for synaptic transmission and behavior in Drosophila melanogaster
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Abstract
In this thesis, I explored the role of alternative splicing of the voltage-gated calcium channel cacophony in Drosophila melanogaster with special focus on its role in synaptic transmission. I could show that the functional diversity of cacophony, which is homologous to the CaV2 channel family in vertebrates, relies heavily on alternative splicing of two splicing sites, one in the voltage sensor and one with a binding site for accessory subunits.
My acquired data demonstrate that evoked synaptic vesicle release is possible only with one of the two alternative exons in the voltage sensor of the first homologous repeat, namely IS4B. My data provide evidence that isoforms with the other alternative exon, IS4A, are not required and not sufficient for normal synaptic transmission. Still, animals lacking exon IS4A show a severely impaired behavior and life expectancy is extremely reduced. As for the other investigated splice site, the binding site for accessory subunits in the intracellular loop between homologous repeats I and II, animals with a homozygous loss of either exon are still viable. Although loss of the exon I-IIB results in a reduced synaptic transmission amplitude, this does not result in an effect on motor behavior or life expectancy.