Regulation of retrograde signaling at neuromuscular junctions by the novel C2 domain protein AEX-1

Neuron. 2002 Jan 17;33(2):249-59. doi: 10.1016/s0896-6273(01)00587-6.


Retrograde signaling from postsynaptic cells to presynaptic neurons is essential for regulation of synaptic development, maintenance, and plasticity. Here we report that the novel protein AEX-1 controls retrograde signaling at neuromuscular junctions in C. elegans. aex-1 mutants show neural defects including reduced presynaptic activity and abnormal localization of the synaptic vesicle fusion protein UNC-13. Muscle-specific AEX-1 expression rescues these defects but neuron-specific expression does not. AEX-1 has an UNC-13 homologous domain and appears to regulate exocytosis in muscles. This retrograde signaling requires prohormone-convertase function in muscles, suggesting that a peptide is the retrograde signal. This signal regulates synaptic vesicle release via the EGL-30 Gq(alpha) protein at presynaptic terminals.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins*
  • Carrier Proteins
  • Endopeptidases / physiology
  • Helminth Proteins / metabolism
  • Intestines / physiology
  • Molecular Sequence Data
  • Muscle, Skeletal / physiology
  • Mutation / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / physiology*
  • Nervous System Malformations / genetics
  • Nervous System Physiological Phenomena
  • Neuromuscular Junction / physiology*
  • Phenotype
  • Presynaptic Terminals / physiology
  • Signal Transduction / physiology*
  • Synapses / metabolism
  • Synaptic Transmission / physiology


  • AEX-1 protein, C elegans
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Helminth Proteins
  • Nerve Tissue Proteins
  • phorbol ester binding protein
  • AEX-5 prohormone convertase
  • Endopeptidases

Associated data

  • GENBANK/AF324832