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

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.

Citation

Wesley L Hung, Christine Hwang, Shangbang Gao, Edward H Liao, Jyothsna Chitturi, Ying Wang, Hang Li, Christian Stigloher, Jean-Louis Bessereau, Mei Zhen. Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development. The EMBO journal. 2013 Jun 12;32(12):1745-60

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PMID: 23665919

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