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Published online
doi:10.1083/jcb.200712152
The Journal of Cell Biology, Vol. 181, No. 1, 157-170
The Rockefeller University Press, 0021-9525 $30.00
© Ly et al.
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Article

straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel {alpha}1 subunit



Cindy V. Ly1, Chi-Kuang Yao2,3, Patrik Verstreken2,3, Tomoko Ohyama2, and Hugo J. Bellen1,2,3,4

1 Department of Neuroscience, 2 Department of Molecular and Human Genetics, 3 Howard Hughes Medical Institute, and 4 Program in Developmental Biology, Baylor College of Medicine, Houston, TX 77030

Correspondence to H. Bellen: hbellen{at}bcm.tmc.edu

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} Ca2+ channel subunit in mediating the proper localization of an {alpha}1 subunit at synapses.

P. Verstreken's present address is VIB Department of Developmental Genetics, K.U. Leuven Center for Human Genetics, 3000 Leuven, Belgium.

Abbreviations used in this paper: Brp, Bruchpilot; Cac, Cacophony; CPG, central pattern generator; EJP, excitatory junctional potential; ERG, electroretinogram; mEJP, miniature EJP; NMJ, neuromuscular junction; PR, photoreceptor; SSR, subsynaptic reticulum; stj, straightjacket; TEM, transmission electron microscopy; TTX, tetrodotoxin; VGCC, voltage-gated calcium channel; VNC, ventral nerve cord; VWA, von Willebrand factor A.


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