Nemo kinase interacts with Mad to coordinate synaptic growth at the Drosophila neuromuscular junction.
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.
Merino
Carlos
C
Department of Physiology, McGill University, Montréal, Québec, Canada H3G 1Y6.
Penney
Jay
J
González
Miranda
M
Tsurudome
Kazuya
K
Moujahidine
Myriam
M
O'Connor
Michael B
MB
Verheyen
Esther M
EM
Haghighi
Pejmun
P
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*
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