title: Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila.
abstract: Toll-like receptors (TLRs) are best characterized for their roles in mediating dorsoventral patterning and the innate immune response. However, recent studies indicate that TLRs are also involved in regulating neuronal growth and development. Here, we demonstrate that the TLR Tollo positively regulates growth of the Drosophila melanogaster larval neuromuscular junction (NMJ). Tollo mutants exhibited NMJ undergrowth, whereas increased expression of Tollo led to NMJ overgrowth. Tollo expression in the motoneuron was both necessary and sufficient for regulating NMJ growth. Dominant genetic interactions together with altered levels of phosphorylated c-Jun N-terminal kinase (JNK) and puc-lacZ expression revealed that Tollo signals through the JNK pathway at the NMJ. Genetic interactions also revealed that the neurotrophin Spätzle3 (Spz3) is a likely Tollo ligand. Spz3 expression in muscle and proteolytic activation via the Easter protease was necessary and sufficient to promote NMJ growth. These results demonstrate the existence of a novel neurotrophin signaling pathway that is required for synaptic development in Drosophila.
authors.affiliation: Laboratory of Genetics, University of Wisconsin-Madison, Madison, WI 53705.
authors.forename: Shannon L
authors.initials: SL
authors.lastname: Ballard
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Miller
authors.forename: Barry
authors.initials: B
authors.lastname: Ganetzky
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology*; D015870:Gene Expression; D005786:Gene Expression Regulation; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D007814:Larva / Q000166:cytology; D009046:Motor Neurons / Q000502:physiology / Q000648:ultrastructure; D009469:Neuromuscular Junction / Q000502:physiology / Q000648:ultrastructure; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D029721:Drosophila Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; C000588484:Spz3 protein, Drosophila; C000588485:Tollo protein, Drosophila; D048031:JNK Mitogen-Activated Protein Kinases