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Attenuation of insulin signalling contributes to FSN‐1‐mediated regulation of synapse development
Author(s) -
Hung Wesley L,
Hwang Christine,
Gao ShangBang,
Liao Edward H,
Chitturi Jyothsna,
Wang Ying,
Li Hang,
Stigloher Christian,
Bessereau JeanLouis,
Zhen Mei
Publication year - 2013
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2013.91
Subject(s) - biology , signalling , synapse , microbiology and biotechnology , insulin , signal transduction , insulin receptor , neuroscience , endocrinology , insulin resistance
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.