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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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F-Box Proteins / genetics
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F-Box Proteins / metabolism*
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HEK293 Cells
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Humans
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Insulin / genetics
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Insulin / metabolism*
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MAP Kinase Kinase Kinases / genetics
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MAP Kinase Kinase Kinases / metabolism
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MAP Kinase Signaling System / physiology*
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Muscles / metabolism*
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Mutation
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Proprotein Convertase 2 / genetics
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Proprotein Convertase 2 / metabolism
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Somatomedins / genetics
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Somatomedins / metabolism
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Synapses / genetics
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Synapses / metabolism*
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Ubiquitination / physiology
Substances
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Caenorhabditis elegans Proteins
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F-Box Proteins
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FSN-1 protein, C elegans
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Insulin
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Somatomedins
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DLK-1 protein, C elegans
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MAP Kinase Kinase Kinases
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EGL-3 proprotein convertase, C elegans
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Proprotein Convertase 2