Reference - Detail
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 |
WOS Category | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
Resource | |
C.elegans | tm2308 tm1888 tm4467 tm2560 tm2416 tm907 tm4144 tm3498 tm1053 tm2918 tm4856 tm4886 tm790 tm339 tm5155 tm1947 tm5180 tm1875 tm1983 tm1922 tm1053 tm2988 tm3095 tm2632 |