Mutations in a Drosophila α2δ voltage-gated calcium channel subunit reveal a crucial synaptic function

Dion K. Dickman, Peri T. Kurshan, Thomas L. Schwarz

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Voltage-dependent calcium channels regulate many aspects of neuronal biology, including synaptic transmission. In addition to their α1 subunit, which encodes the essential voltage gate and selective pore, calcium channels also contain auxiliary α 2δ, β, and γsubunits. Despite progress in understanding the biophysical properties of calcium channels, the in vivo functions of these auxiliary subunits remain unclear. We have isolated mutations in the gene encoding an α2δ calcium channel subunit (dα2δ-3) using a forward genetic screen in Drosophila. Null mutations in this gene are embryonic lethal and can be rescued by expression in the nervous system, demonstrating that the essential function of this subunit is neuronal. The photoreceptor phenotype of dα 2δ-3 mutants resembles that of the calcium channel α1 mutant cacophony (cac), suggesting shared functions. We have examined in detail genotypes that survive to the third-instar stage. Electrophysiological recordings demonstrate that synaptic transmission is severely impaired in these mutants. Thus the α2δ calcium channel subunit is critical for calcium-dependent synaptic function. As such, this Drosophila isoform is the likely partner to the presynaptic calcium channel α1 subunit encoded by the cac locus. Consistent with this hypothesis, cacGFP fluorescence at the neuromuscular junction is reduced in dα2δ-3 mutants. This is the first characterization of an α2δ-3 mutant in any organism and indicates a necessary role for α2δ-3 in presynaptic vesicle release and calcium channel expression at active zones.

Original languageEnglish (US)
Pages (from-to)31-38
Number of pages8
JournalJournal of Neuroscience
Volume28
Issue number1
DOIs
StatePublished - Jan 2 2008
Externally publishedYes

Fingerprint

Calcium Channels
Drosophila
Mutation
Synaptic Transmission
Lethal Genes
Neuromuscular Junction
Nervous System
Protein Isoforms
Fluorescence
Genotype
Calcium
Phenotype
Genes

Keywords

  • Active zone
  • Bouton
  • Calcium channel
  • Drosophila
  • Neuromuscular junction
  • Synaptic transmission

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mutations in a Drosophila α2δ voltage-gated calcium channel subunit reveal a crucial synaptic function. / Dickman, Dion K.; Kurshan, Peri T.; Schwarz, Thomas L.

In: Journal of Neuroscience, Vol. 28, No. 1, 02.01.2008, p. 31-38.

Research output: Contribution to journalArticle

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