Postsynaptic TGF-β Signaling

Science's STKE  11 Apr 2006:
Vol. 2006, Issue 330, pp. tw122
DOI: 10.1126/stke.3302006tw122

Dudu et al. used Drosophila larval neuromuscular junction (NMJ) as a synaptic model in which to study transforming growth factor-β (TGF-β) signaling. A TGF-β retrograde signal is a well-known pathway involved in Drosophila NMJ development, but new evidence suggests a role for TGF-β signaling in muscle cells as well. Dudu et al. show by immunostaining that the type I TGF-β receptor called Thick veins (Tkv) and the receptor-regulated Smad (R-Smad) called Mothers against Dpp (Mad) are present in the postsynaptic subsynaptic reticulum. Endogenous phosphorylated Mad was found in both the postsynaptic density and the nuclei of the muscles, and expression of a constitutively active Tkv increased the abundance of a green fluorescent protein (GFP)-Mad fusion protein in the nuclei. Stimulation of the muscle with high K+ increased the GFP-Mad associated with the synaptic region. Nuclear trafficking of GFP-Mad was monitored using a fluorescence recovery after photobleaching (FRAP) assay, and the proportion of GFP-Mad that is immobile in the nucleus increased in muscles treated with high K+ or expressing the constitutively active Tkv. This may reflect association of Mad with other factors, thereby preventing its export. It remains to be determined whether TGF-β ligands are released from the presynaptic side during neurotransmission or whether the ligands released from the muscle are acting as autocrine factors to coordinate nerve-muscle development.

V. Dudu, T. Bittig, E. Entchev, A. Kicheva, F. Jülicher, M. González-Gaitán, Postsynaptic Mad signaling at the Drosophila neuromuscular junction. Curr. Biol. 16, 625-635 (2006). [PubMed]