Department of Biology, The University of Iowa, Iowa City, IA 52242, USA.
J Neurosci. 2010 Nov 24;30(47):15821-33. doi: 10.1523/JNEUROSCI.3448-10.2010.
Synapse formation is tightly associated with neuronal excitability. We found striking synaptic overgrowth caused by Drosophila K(+)-channel mutations of the seizure and slowpoke genes, encoding Erg and Ca(2+)-activated large-conductance (BK) channels, respectively. These mutants display two distinct patterns of "satellite" budding from larval motor terminus synaptic boutons. Double-mutant analysis indicates that BK and Erg K(+) channels interact with separate sets of synaptic proteins to affect distinct growth steps. Post-synaptic L-type Ca(2+) channels, Dmca1D, and PSD-95-like scaffold protein, Discs large, are required for satellite budding induced by slowpoke and seizure mutations. Pre-synaptic cacophony Ca(2+) channels and the NCAM-like adhesion molecule, Fasciclin II, take part in a maturation step that is partially arrested by seizure mutations. Importantly, slowpoke and seizure satellites were both suppressed by rutabaga mutations that disrupt Ca(2+)/CaM-dependent adenylyl cyclase, demonstrating a convergence of K(+) channels of different functional categories in regulation of excitability-dependent Ca(2+) influx for triggering cAMP-mediated growth plasticity.
突触形成与神经元兴奋性密切相关。我们发现果蝇 K(+)通道突变体 seizure 和 slowpoke 基因的惊人的突触过度生长,分别编码 erg 和 Ca(2+)-激活的大电导 (BK) 通道。这些突变体显示出两种不同的“卫星”芽从幼虫运动终末突触小泡的模式。双突变体分析表明,BK 和 erg K(+)通道与不同的突触蛋白相互作用,影响不同的生长步骤。L-型 Ca(2+)通道、Dmca1D 和 PSD-95 样支架蛋白 Discs large 在后突触区是 slowpoke 和 seizure 突变诱导的卫星芽生所必需的。在 Ca(2+)依赖性钙调蛋白依赖性腺苷酸环化酶破坏的 rutabaga 突变中,cacophony Ca(2+)通道和神经细胞黏附分子 Fasciclin II 参与了成熟步骤,该步骤部分被 seizure 突变所阻断。重要的是,slowpoke 和 seizure 卫星都被 rutabaga 突变所抑制,rutabaga 突变破坏了 Ca(2+)/CaM 依赖性腺苷酸环化酶,这表明不同功能类别的 K(+)通道在调节兴奋性依赖的 Ca(2+)内流以触发 cAMP 介导的生长可塑性方面的汇聚。