RRC ID 45992
Author Hung WL, Hwang C, Gao S, Liao EH, Chitturi J, Wang Y, Li H, Stigloher C, Bessereau JL, Zhen M.
Title Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development.
Journal EMBO J
Abstract 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.
Volume 32(12)
Pages 1745-60
Published 2013-6-12
DOI 10.1038/emboj.2013.91
PII emboj201391
PMID 23665919
PMC PMC3680742
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* F-Box Proteins / genetics F-Box Proteins / metabolism* HEK293 Cells Humans Insulin / genetics Insulin / metabolism* MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism MAP Kinase Signaling System / physiology* Muscles / metabolism* Mutation Proprotein Convertase 2 / genetics Proprotein Convertase 2 / metabolism Somatomedins / genetics Somatomedins / metabolism Synapses / genetics Synapses / metabolism* Ubiquitination / physiology
IF 9.889
Times Cited 11
C.elegans tm5180 tm1875 tm1983 tm1922 tm1053 tm2988 tm3095 tm2632 tm2308 tm1888 tm4467 tm2560 tm2416 tm907 tm4144 tm3498 tm1053 tm2918 tm4856 tm4886 tm790 tm339 tm5155 tm1947