1. Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction
- Author
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Nobuaki Maeda, Keisuke Kamimura, Jun Nakagawa, Kohei Ueno, Rie Hamada, and Minoru Saitoe
- Subjects
Frizzled ,endocrine system ,Neuromuscular Junction ,Perlecan ,Wnt1 Protein ,Biology ,Neuromuscular junction ,Article ,Microscopy, Electron, Transmission ,Postsynaptic potential ,medicine ,Animals ,Drosophila Proteins ,Wnt Signaling Pathway ,Research Articles ,fungi ,Wnt signaling pathway ,Cell Biology ,biology.organism_classification ,Cell biology ,carbohydrates (lipids) ,medicine.anatomical_structure ,Drosophila melanogaster ,nervous system ,Larva ,Mutation ,biology.protein ,Signal transduction ,Drosophila Protein ,Heparan Sulfate Proteoglycans - Abstract
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.
- Published
- 2013