Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction.
Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction.
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DOI：
10.1083/jcb.201207036
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发表时间：
2013-01-21
期刊：
影响因子：
--
通讯作者：
Maeda N
中科院分区：
文献类型：
--
作者：
Kamimura K;Ueno K;Nakagawa J;Hamada R;Saitoe M;Maeda N
神经肌肉接头处的基底膜蛋白聚糖/Trol 抑制突触前典型 Wg 信号传导，但增强突触后卷曲核输入途径。硫酸乙酰肝素蛋白聚糖 (HSPG) 在多种组织中 Wnt 信号传导活性的调节中发挥着关键作用。在果蝇神经肌肉接头 (NMJ)，Wnt/Wingless (Wg) 调节突触前和突触后结构的形成；然而，平衡这种双向信号的机制仍然难以捉摸。在本文中，我们证明了分泌型 HSPG、基底膜蛋白聚糖/trol 基因的突变导致了多种突触后缺陷和 NMJ 处突触纽扣的过度产生。突触后缺陷，例如突触亚网（SSR）减少，可以通过卷曲核输入 Wg 通路的突触后激活来挽救。相比之下，突触 bouton 的过量产生受到典型 Wg 通路突触前下调的抑制。我们还表明 Trol 位于 SSR 中并促进细胞外 Wg 蛋白的突触后积累。这些结果表明，Trol 通过在 NMJ 精确分配 Wg 来双向调节 Wg 的突触前和突触后活动。
Perlecan/Trol at the neuromuscular junction suppresses presynaptic canonical Wg signaling but enhances the postsynaptic Frizzled nuclear import pathway. Heparan sulfate proteoglycans (HSPGs) play pivotal roles in the regulation of Wnt signaling activity in several tissues. At the Drosophila melanogaster neuromuscular junction (NMJ), Wnt/Wingless (Wg) regulates the formation of both pre- and postsynaptic structures; however, the mechanism balancing such bidirectional signaling remains elusive. In this paper, we demonstrate that mutations in the gene of a secreted HSPG, perlecan/trol, resulted in diverse postsynaptic defects and overproduction of synaptic boutons at NMJ. The postsynaptic defects, such as reduction in subsynaptic reticulum (SSR), were rescued by the postsynaptic activation of the Frizzled nuclear import Wg pathway. In contrast, overproduction of synaptic boutons was suppressed by the presynaptic down-regulation of the canonical Wg pathway. We also show that Trol was localized in the SSR and promoted postsynaptic accumulation of extracellular Wg proteins. These results suggest that Trol bidirectionally regulates both pre- and postsynaptic activities of Wg by precisely distributing Wg at the NMJ.
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影响因子：
2.7
作者：
Guha, Arjun;Lin, Li;Kornberg, Thomas B.
通讯作者：
Kornberg, Thomas B.
影响因子：
16.2
作者：
Ataman, Bulent;Ashley, James;Budnik, Vivian
通讯作者：
Budnik, Vivian
影响因子：
11.8
作者：
Kreuger, J;Perez, L;Cohen, SM
通讯作者：
Cohen, SM
DOI：
10.1046/j.1432-1327.2000.01337.x
发表时间：
2000-06-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Friedrich, MVK;Schneider, M;Baumgartner, S
通讯作者：
Baumgartner, S
影响因子：
5.7
作者：
Budnik V;Salinas PC
通讯作者：
Salinas PC