title: Perlecan regulates bidirectional Wnt signaling at the Drosophila neuromuscular junction.
abstract: 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.
authors: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo 156-8506, Japan.
authors: Keisuke
authors: K
authors: Kamimura
authors: Kohei
authors: K
authors: Ueno
authors: Jun
authors: J
authors: Nakagawa
authors: Rie
authors: R
authors: Hamada
authors: Minoru
authors: M
authors: Saitoe
authors: Nobuaki
authors: N
authors: Maeda
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000254:growth & development / Q000378:metabolism*; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007814:Larva / Q000254:growth & development / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D009154:Mutation; D009469:Neuromuscular Junction / Q000254:growth & development / Q000378:metabolism* / Q000648:ultrastructure; D060449:Wnt Signaling Pathway; D051155:Wnt1 Protein / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D019812:Heparan Sulfate Proteoglycans; D051155:Wnt1 Protein; C472788:trol protein, Drosophila; C074622:wg protein, Drosophila; C071927:perlecan