Author : Kimberly Young
Publisher :
Page : pages
File Size : 10,7 MB
Release : 2016
Category :
ISBN :
"Retrograde Bone Morphogenic Protein (BMP) signalling is essential for the coordinated growth of neuromuscular junction synapses in Drosophila motor neurons: postsynaptic release of a BMP ligand triggers a retrograde cascade, which culminates in the phosphorylation and nuclear translocation of the transcription factor Mad and the downstream transcription of BMP target genes. We have previously reported that Nemo (Nmo) Kinase phosphorylates Mad at a site distinct from BMP receptor phosphorylation, thereby modulating the normal accumulation of Mad. Nmo mutants display severe defects in synaptic structural growth but curiously retain normal levels of synaptic transmission. Interestingly, it was found that overactivation of Nmo negatively affects synaptic function but not the synaptic structure. Combining fly genetics with electrophysiology and imaging, we set out to investigate how Nmo alternatively regulates BMP signalling at neuromuscular junction synapses. Overactivation of a phosphomimetic Mad transgene is found to diminish synaptic function, suggesting that larval neurotransmission is sensitive to Nemo phosphorylated Mad. In a nmo mutant background, overexpression of a Mad transgene augments synaptic function, whereas a phosphomimetic Mad transgene reduces synaptic function. These modulations of synaptic function are in accordance with live-imaging data, which suggest that overactivation of Nmo reduces the residency time of nuclear Mad, most likely through an increase in the rate of nuclear export of Mad. In sum, Nemo Kinase modulates the BMP pathway through the localization of Mad to ensure normal synaptic growth and function." --