straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel alpha1 subunit.
In a screen to identify genes involved in synaptic function, we isolated mutations in Drosophila melanogaster straightjacket (stj), an alpha(2)delta 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 alpha(1) subunit in D. melanogaster. Interestingly, neuronal overexpression of cac partially rescues the viability and physiological defects in stj mutants, indicating a role for the alpha(2)delta Ca(2+) channel subunit in mediating the proper localization of an alpha(1) subunit at synapses.
Ly
Cindy V
CV
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Yao
Chi-Kuang
CK
Verstreken
Patrik
P
Ohyama
Tomoko
T
Bellen
Hugo J
HJ
D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D004596:Electroretinography; D009154:Mutation; D009474:Neurons / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D013569:Synapses
D015220:Calcium Channels; D029721:Drosophila Proteins; D018377:Neurotransmitter Agents; C472405:cac protein, Drosophila; C528236:stj protein, Drosophila