title: Nemo kinase interacts with Mad to coordinate synaptic growth at the Drosophila neuromuscular junction.
abstract: Bone morphogenic protein (BMP) signaling is essential for the coordinated assembly of the synapse, but we know little about how BMP signaling is modulated in neurons. Our findings indicate that the Nemo (Nmo) kinase modulates BMP signaling in motor neurons. nmo mutants show synaptic structural defects at the Drosophila melanogaster larval neuromuscular junction, and providing Nmo in motor neurons rescues these defects. We show that Nmo and the BMP transcription factor Mad can be coimmunoprecipitated and find a genetic interaction between nmo and Mad mutants. Moreover, we demonstrate that Nmo is required for normal distribution and accumulation of phosphorylated Mad in motor neurons. Finally, our results indicate that Nmo phosphorylation of Mad at its N terminus, distinct from the BMP phosphorylation site, is required for normal function of Mad. Based on our findings, we propose a model in which phosphorylation of Mad by Nmo ensures normal accumulation and distribution of Mad and thereby fine tunes BMP signaling in motor neurons.
authors.affiliation: Department of Physiology, McGill University, Montréal, Québec, Canada H3G 1Y6.
authors.forename: Carlos
authors.initials: C
authors.lastname: Merino
authors.forename: Jay
authors.initials: J
authors.lastname: Penney
authors.forename: Miranda
authors.initials: M
authors.lastname: González
authors.forename: Kazuya
authors.initials: K
authors.lastname: Tsurudome
authors.forename: Myriam
authors.initials: M
authors.lastname: Moujahidine
authors.forename: Michael B
authors.initials: MB
authors.lastname: O'Connor
authors.forename: Esther M
authors.initials: EM
authors.lastname: Verheyen
authors.forename: Pejmun
authors.initials: P
authors.lastname: Haghighi
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology*; D009046:Motor Neurons; D009469:Neuromuscular Junction; D010766:Phosphorylation; D013569:Synapses; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; C110707:nmo protein, Drosophila