Straightjacket is required for the synaptic stabilization of Cacophony, a voltage-gated calcium channel alpha1 subunit (JCB, 2008)

In a screen to identify genes involved in synaptic function, we isolated mutations in Drosophila melanogaster straightjacket (stj), an α₂δ subunit of the voltage-gated calcium channel. stj mutant photoreceptors develop normal synaptic connections but display reduced “on–off” transients in electroretinogram recordings, indicating a failure to evoke postsynaptic responses and, thus, a defect in neurotransmission. stj is expressed in neurons but excluded from glia. Mutants exhibit endogenous seizure-like activity, indicating altered neuronal excitability. However, at the synaptic level, stj larval neuromuscular junctions exhibit approximately fourfold reduction in synaptic release compared with controls stemming from a reduced release probability at these synapses. These defects likely stem from destabilization of Cacophony (Cac), the primary presynaptic α₁ subunit in D. melanogaster. Interestingly, neuronal overexpression of cac partially rescues the viability and physiological defects in stj mutants, indicating a role for the α₂δ Ca²⁺ channel subunit in mediating the proper localization of an α₁ subunit at synapses.