Regulation of retrograde signaling at neuromuscular junctions by the novel C2 domain protein AEX-1.
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.
Doi
Motomichi
M
Laboratory of Molecular Neurobiology, Neuroscience Research Institute AIST, Tsukuba, 305-8566, Japan.
Iwasaki
Kouichi
K
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D010450:Endopeptidases / Q000502:physiology; D015801:Helminth Proteins / Q000378:metabolism; D007422:Intestines / Q000502:physiology; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009421:Nervous System Malformations / Q000235:genetics; D009424:Nervous System Physiological Phenomena; D009469:Neuromuscular Junction / Q000502:physiology*; D010641:Phenotype; D017729:Presynaptic Terminals / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
C446288:AEX-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D015801:Helminth Proteins; D009419:Nerve Tissue Proteins; C083141:phorbol ester binding protein; C446289:AEX-5 prohormone convertase; D010450:Endopeptidases