Abstract
Retrograde signaling from postsynaptic cells to presynaptic neurons is essential for regulation of synaptic development, maintenance, and plasticity. Membrane-permeable molecules, such as gases and lipids, are well known candidates for retrograde signals. Recent studies suggest that secreted molecules also may act as retrograde signals. However, the molecular mechanism of the retrograde-signal release from postsynaptic cells is largely unknown. Here we report that a peptidic retrograde signal functions at neuromuscular junctions in C. elegans and the novel C2 domain protein AEX-1 regulates the signal release from muscle.
aex-1 mutants show several neural defective phenotypes such as reduced Ach transmission and abnormal localization of the synaptic vesicle fusion protein UNC-13. Contrary to these phenotypes, we found that aex-1 is predominantly expressed in muscles and intestine. Our experiments showed that muscle-specific AEX-1 expression rescues some of neural defects including abnormal presynaptic UNC-13 localization, but neuron-specific expression does not, suggesting that AEX-1 regulates neural activities from muscles. Furthermore, in muscles, this signaling pathway requires the AEX-5 prohormone convertase, which processes prohormone maturation, suggesting that a peptide is the retrograde signal in this pathway. AEX-1 protein has a C2 domain and a UNC-13 homology domain, and this protein and its vertebrate homologues appear to regulate exocytosis. Our results indicate the presence of a general mechanism in muscle to modulate neural activities, such as the synaptic transmission efficacy by AEX-1. [Jpn J Physiol 54 Suppl:S32 (2004)]
