EMBO reports, 2023-06, Vol.24 (6), p.e55556-n/a
2023
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- Autor(en) / Beteiligte
- Titel
- Changes in lipid metabolism driven by steroid signalling modulate proteostasis in C. elegans
- Ist Teil von
- EMBO reports, 2023-06, Vol.24 (6), p.e55556-n/a
- Ort / Verlag
- England: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2023
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- Alzheimer's, Parkinson's and Huntington's diseases can be caused by mutations that enhance protein aggregation, but we still do not know enough about the molecular players of these pathways to develop treatments for these devastating diseases. Here, we screen for mutations that might enhance aggregation in Caenorhabditis elegans, to investigate the mechanisms that protect against dysregulated homeostasis. We report that the stomatin homologue UNC‐1 activates neurohormonal signalling from the sulfotransferase SSU‐1 in ASJ sensory/endocrine neurons. A putative hormone, produced in ASJ, targets the nuclear receptor NHR‐1, which acts cell autonomously in the muscles to modulate polyglutamine repeat (polyQ) aggregation. A second nuclear receptor, DAF‐12, functions oppositely to NHR‐1 to maintain protein homeostasis. Transcriptomics analyses of unc‐1 mutants revealed changes in the expression of genes involved in fat metabolism, suggesting that fat metabolism changes, controlled by neurohormonal signalling, contribute to protein homeostasis. Furthermore, the enzymes involved in the identified signalling pathway are potential targets for treating neurodegenerative diseases caused by disrupted protein homeostasis. Synopsis A neurohormonal signal emanating from Caenorhabditis elegans ASJ neurons modulates protein homeostasis in the body wall muscles. The signal depends on the stomatin homologue UNC‐1 in neurons and the nuclear receptor NHR‐1 in muscles. Electrical synapse disruption modulates protein homeostasis in a non‐cell autonomous manner in C. elegans. PolyQ aggregation in muscles is modulated by a neurohormonal signal involving the sulfotransferase SSU‐1 and sulfatases SUL‐2 and SUL‐3. The nuclear receptor NHR‐1 is a transcription factor that regulates lipid gene expression to modulate proteostasis in the muscle. A neurohormonal signal emanating from Caenorhabditis elegans ASJ neurons modulates protein homeostasis in the body wall muscles. The signal depends on the stomatin homologue UNC‐1 in neurons and the nuclear receptor NHR‐1 in muscles.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1469-221XeISSN: 1469-3178DOI: 10.15252/embr.202255556Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10240203
- Format
- –
- Schlagworte
- Alzheimer's disease, Animals, Body wall, Caenorhabditis elegans, Caenorhabditis elegans - genetics, Caenorhabditis elegans - metabolism, Caenorhabditis elegans Proteins - genetics, Caenorhabditis elegans Proteins - metabolism, Fat metabolism, Gene expression, Homeostasis, Homology, Huntingtons disease, Lipid metabolism, Lipid Metabolism - genetics, Lipids, Movement disorders, Muscles, Mutation, Neurodegenerative diseases, Neurons, nuclear receptors, Parkinson's disease, Polyglutamine, protein aggregation, Protein interaction, Proteins, Proteostasis, Receptors, Receptors, Cytoplasmic and Nuclear - metabolism, Sensory neurons, Signal transduction, Signaling, steroid hormone signalling, Steroids - metabolism, Sulfotransferase, Transcriptomics, Trinucleotide repeat diseases