straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel alpha1 subunit.
straightjacket is required for the synaptic stabilization of cacophony, a voltage-gated calcium channel alpha1 subunit.
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DOI：
10.1083/jcb.200712152
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发表时间：
2008-04-07
影响因子：
7.8
通讯作者：
Bellen, Hugo J.
中科院分区：
文献类型：
--
作者：
Ly, Cindy V.;Yao, Chi-Kuang;Verstreken, Patrik;Ohyama, Tomoko;Bellen, Hugo J.
在一项筛选中，我们分离出了黑腹果蝇straightjacket（stj）中的突变，该突变是电压门控钙通道的α2δ亚基。STJ突变型光感受器形成正常的突触连接，但在视网膜电图记录中显示减少的“开-关”瞬变，表明不能引起突触后反应，因此，神经传递有缺陷。STJ在神经元中表达，但在神经胶质中不表达。突变体表现出内源性神经元样活性，表明神经元兴奋性改变。然而，在突触水平上，stj幼虫神经肌肉接头表现出约四倍的突触释放减少相比，控制源于在这些突触的释放概率降低。这些缺陷可能源于D中主要突触前α1亚基Cacophony（Cac）的不稳定。黑腹菌有趣的是，cac的神经元过表达部分地挽救了stj突变体中的活力和生理缺陷，表明α2δ Ca 2+通道亚基在介导α1亚基在突触处的适当定位中的作用。
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.
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