Multiple hormonal signalling pathways function cell-nonautonomously to control protein homeostasis in Caenorhabditis elegans

Gomez Escribano, A. P.; Bono-Yague, J.; Roca, M.; Panadero, J.; Sequedo, M. D.; Saini, R.; Knoelker, H.-J.; Blanca, J. M.; Burguera, J. A.; Lahoz, A.; Canizares, J.; Millan, J. M.; Burton, N.; Vazquez-Manrique, R.

doi:10.1101/551580

bioRxiv · 10.1101/551580

Multiple hormonal signalling pathways function cell-nonautonomously to control protein homeostasis in Caenorhabditis elegans

Gomez Escribano, A. P.·Bono-Yague, J.·Roca, M.·Panadero, J.·Sequedo, M. D.·Saini, R.·Knoelker, H.-J.·Blanca, J. M.·Burguera, J. A.·Lahoz, A.·Canizares, J.·Millan, J. M.·Burton, N.·Vazquez-Manrique, R.

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Abstract

Protein homeostasis is crucial for viability of all organisms, and mutations that enhance protein aggregation cause different human pathologies, including polyglutamine (polyQ) diseases, such as some spinocerebellar ataxias or Huntington disease. Here, we report that neuronal Stomatin-like protein UNC-1 protects against aggregation of prone-to-aggregate proteins, like polyQs, -synuclein and {beta}-amyloid, in C. elegans. UNC-1, in IL2 neurons, antagonizes the function of the cytosolic sulfotransferase SSU-1 in neurohormonal signalling from ASJ neurons. The target of this hormone is the nuclear hormone receptor NHR-1, which acts cell-autonomously to protect from aggregation in muscles. A second nuclear hormone receptor, DAF-12, functions oppositely to NHR-1 to maintain protein homeostasis. Transcriptomics analyses reveal deep changes in the expression of genes involved in fat metabolism, in unc-1 mutants, which are regulated by NHR-1. This suggest that fat metabolism changes, controlled by neurohormonal signalling, contributes to modulate protein homeostasis.

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Gomez Escribano, A. P., Bono-Yague, J., Roca, M., Panadero, J., Sequedo, M. D., Saini, R., Knoelker, H.-J., Blanca, J. M., Burguera, J. A., Lahoz, A., Canizares, J., Millan, J. M., Burton, N., Vazquez-Manrique, R.. 2019-02-15. Multiple hormonal signalling pathways function cell-nonautonomously to control protein homeostasis in Caenorhabditis elegans. https://doi.org/10.1101/551580

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