Postsynaptic mad signaling at the Drosophila neuromuscular junction

Curr Biol. 2006 Apr 4;16(7):625-35. doi: 10.1016/j.cub.2006.02.061.


Background: Cell-to-cell communication at the synapse involves synaptic transmission as well as signaling mediated by growth factors, which provide developmental and plasticity cues. There is evidence that a retrograde, presynaptic transforming growth factor-beta (TGF-beta) signaling event regulates synapse development and function in Drosophila.

Results: Here we show that a postsynaptic TGF-beta signaling event occurs during larval development. The type I receptor Thick veins (Tkv) and the R-Smad transcription factor Mothers-against-dpp (Mad) are localized postsynaptically in the muscle. Furthermore, Mad phosphorylation occurs in regions facing the presynaptic active zones of neurotransmitter release within the postsynaptic subsynaptic reticulum (SSR). In order to monitor in real time the levels of TGF-beta signaling in the synapse during synaptic transmission, we have established a FRAP assay to measure Mad nuclear import/export in the muscle. We show that Mad nuclear trafficking depends on stimulation of the muscle.

Conclusions: Our data suggest a mechanism linking synaptic transmission and postsynaptic TGF-beta signaling that may coordinate nerve-muscle development and function.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • DNA-Binding Proteins / analysis
  • DNA-Binding Proteins / metabolism*
  • Drosophila / growth & development
  • Drosophila / metabolism*
  • Drosophila Proteins / analysis
  • Drosophila Proteins / metabolism*
  • Fluorescence Recovery After Photobleaching / methods
  • Kinetics
  • Larva / cytology
  • Larva / metabolism
  • Ligands
  • Models, Biological
  • Muscles / cytology
  • Neuromuscular Junction / growth & development
  • Neuromuscular Junction / metabolism*
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / analysis
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Cell Surface / analysis
  • Receptors, Cell Surface / metabolism
  • Signal Transduction*
  • Smad Proteins, Receptor-Regulated / metabolism
  • Transcription Factors / analysis
  • Transcription Factors / metabolism*
  • Transforming Growth Factor beta / metabolism*


  • DNA-Binding Proteins
  • Drosophila Proteins
  • Ligands
  • MAD protein, Drosophila
  • Receptors, Cell Surface
  • Smad Proteins, Receptor-Regulated
  • Transcription Factors
  • Transforming Growth Factor beta
  • tkv protein, Drosophila
  • Protein-Serine-Threonine Kinases