Highwire regulates presynaptic BMP signaling essential for synaptic growth
Highwire regulates presynaptic BMP signaling essential for synaptic growth
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DOI：
10.1016/s0896-6273(04)00073-x
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发表时间：
2004-03-25
期刊：
影响因子：
16.2
通讯作者：
Haghighi, AP
中科院分区：
文献类型：
--
作者：
McCabe, BD;Hom, S;Haghighi, AP
Highwire (Hiw) 是一种假定的环指 E3 泛素连接酶，对果蝇神经肌肉接头 (NMJ) 的突触生长有负调节作用。 hiw 突变体具有显着更大的突触尺寸和增加的突触纽扣数量。在这里，我们展示了 Hiw 与 Smad 蛋白 Medea (Med) 结合。 Med 是突触前骨形态发生蛋白 (BMP) 信号级联的一部分，该级联由 Wit、Tkv 和 Sax 三个受体亚基以及 Smad 转录因子 Mad 组成。与野生型相比，BMP 信号传导成分的突变体具有更小的 NMJ 尺寸、减少的神经递质释放和异常的突触超微结构。 BMP 信号突变体抑制 hiw 突变体中突触的过度生长。 BMP 信号传导的激活在野生型中不会引起额外的生长，但在 hiw 突变体中却会导致突触进一步扩张。这些结果揭示了正 BMP 信号传导与 Highwire 负调节之间的平衡，控制着神经肌肉突触的生长。
Highwire (Hiw), a putative RING finger E3 ubiquitin ligase, negatively regulates synaptic growth at the neuromuscular junction (NMJ) in Drosophila. hiw mutants have dramatically larger synaptic size and increased numbers of synaptic boutons. Here we show that Hiw binds to the Smad protein Medea (Med). Med is part of a presynaptic bone morphogenetic protein (BMP) signaling cascade consisting of three receptor subunits, Wit, Tkv, and Sax, in addition to the Smad transcription factor Mad. When compared to wildtype, mutants of BMP signaling components have smaller NMJ size, reduced neurotransmitter release, and aberrant synaptic ultrastructure. BMP signaling mutants suppress the excessive synaptic growth in hiw mutants. Activation of BMP signaling, which in wild-type does not cause additional, growth, in hiw mutants does lead to further synaptic expansion. These results reveal a balance between positive BMP signaling and negative regulation by Highwire, governing the growth of neuromuscular synapses.