Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development

作者:Hung Wesley L; Hwang Christine; Gao ShangBang; Liao Edward H; Chitturi Jyothsna; Wang Ying; Li Hang; Stigloher Christian; Bessereau Jean Louis; Zhen Mei*
来源:The EMBO Journal, 2013, 32(12): 1745-1760.
DOI:10.1038/emboj.2013.91

摘要

A neuronal F-box protein FSN-1 regulates Caenorhabditis elegans neuromuscular junction development by negatively regulating DLK-mediated MAPK signalling. In the present study, we show that attenuation of insulin/IGF signalling also contributes to FSN-1-dependent synaptic development and function. The aberrant synapse morphology and synaptic transmission in fsn-1 mutants are partially and specifically rescued by reducing insulin/IGF-signalling activity in postsynaptic muscles, as well as by reducing the activity of EGL-3, a prohormone convertase that processes agonistic insulin/IGF ligands INS-4 and INS-6, in neurons. FSN-1 interacts with, and potentiates the ubiquitination of EGL-3 in vitro, and reduces the EGL-3 level in vivo. We propose that FSN-1 may negatively regulate insulin/IGF signalling, in part, through EGL-3-dependent insulin-like ligand processing.