Attenuation of insulin signalling contributes to FSN‐1‐mediated regulation of synapse development |
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| Authors: | Wesley L Hung Christine Hwang ShangBang Gao Jyothsna Chitturi Ying Wang Hang Li Jean‐Louis Bessereau Mei Zhen |
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| Institution: | 1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, , Toronto, Ontario, Canada;2. Institute of Medical Science, University of Toronto, , Toronto, Ontario, Canada;3. Institut de Biologie de l’école Normale Supérieure, Biology Department, INSERM, , Paris, France;4. Department of Molecular Genetics, University of Toronto, , Toronto, Ontario, Canada |
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| 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. |
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| Keywords: | fsn‐1 ubiquitin ligase insulin/IGF signalling synapse development |
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