Fig. 3
From: Synapse development and maturation at the drosophila neuromuscular junction
BMP Canonical and Non-Canonical signaling at the NMJ. a BMP canonical signaling includes a paracrine, retrograde mechanism whereby muscle-derived Gbb is released across the synapse where it activates BMPRs Wit and Sax/Tkv triggering internalization. Internalized Gbb is trafficked to the neuronal nucleus where it activates phosphorylation of the Mad to pMad to activate transcription of Trio-GEF promoting overall NMJ growth. A second autocrine canonical pathway involves release of Cmpy bound Gbb from the neuron where it sequestered by α2δ-3, a calcium channel subunit. Neuronally derived Gbb then binds BMPRs and causes transcriptional changes similar to the paracrine canonical pathway to regulate synaptic homeostasis and signal transmission. b BMP non-canonical signaling pathways include those that are Gbb dependent and independent. Gbb dependent non-canonical signaling involves retrograde release of Gbb where it is bound by Wit. LIMK acts as a Wit effector to inhibit Cofilin which normally promotes actin dynamics through filament severing. In a Gbb independent non-canonical mechanism, GluRIIA containing iGluRs form a positive feedback loop with local presynaptic pMad. This mechanism depends on Wit and Sax/Tkv, but not on transcription and is inhibited by Dlp (Glypican)