title: Attenuation of insulin signalling contributes to FSN-1-mediated regulation of synapse development.
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.
authors.affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Wesley L
authors.initials: WL
authors.lastname: Hung
authors.forename: Christine
authors.initials: C
authors.lastname: Hwang
authors.forename: Shangbang
authors.initials: S
authors.lastname: Gao
authors.forename: Edward H
authors.initials: EH
authors.lastname: Liao
authors.forename: Jyothsna
authors.initials: J
authors.lastname: Chitturi
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Li
authors.forename: Christian
authors.initials: C
authors.lastname: Stigloher
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bessereau
authors.forename: Mei
authors.initials: M
authors.lastname: Zhen
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D009132:Muscles / Q000378:metabolism*; D009154:Mutation; D045706:Proprotein Convertase 2 / Q000235:genetics / Q000378:metabolism; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D044783:F-Box Proteins; C530278:FSN-1 protein, C elegans; D007328:Insulin; D013002:Somatomedins; C498050:DLK-1 protein, C elegans; D020930:MAP Kinase Kinase Kinases; C473666:EGL-3 proprotein convertase, C elegans; D045706:Proprotein Convertase 2