Chauve, Laetitia; Hodge, Francesca; Murdoch, Sharlene; Masoudzadeh, Fatemah; Mann, Harry Jack; Lopez-Clavijo, Andrea; Okkenhaug, Hanneke; West, Greg; Sousa, Bebiana C.; Segonds-Pichon, Anne; Li, Cheryl; Wingett, Steven
To survive elevated temperatures, ectotherms adjust the fluidity of membranes by fine-tuning lipid desaturation levels in a process previously described to be cell autonomous. We have discovered that, in Caenorhabditis elegans, neuronal heat shock factor 1 (HSF-1), the conserved master regulator of the heat shock response (HSR), causes extensive fat remodeling in peripheral tissues. These changes include a decrease in fat desaturase and acid lipase expression in the intestine and a global shift in the saturation levels of plasma membrane’s phospholipids. The observed remodeling of plasma membrane is in line with ectothermic adaptive responses and gives worms a cumulative advantage to warm temperatures. We have determined that at least 6 TAX-2/TAX-4 cyclic guanosine monophosphate (cGMP) gated channel expressing sensory neurons, and transforming growth factor ß (TGF-β)/bone morphogenetic protein (BMP) are required for signaling across tissues to modulate fat desaturation. We also find neuronal hsf-1 is not only sufficient but also partially necessary to control the fat remodeling response and for survival at warm temperatures. This is the first study to show that a thermostat-based mechanism can cell nonautonomously coordinate membrane saturation and composition across tissues in a multicellular animal.
We dedicate this work to the memory of Michael J.O. Wakelam. We would like to acknowledge Michael Fasseas (Invermis, Magnitude Biosciences) for plasmid injections and Sunny Biotech for transgenics; Catalina Vallejos and John Marioni for statistical advice at the beginning of the work; Simon Walker, Imaging, Bioinformatics and Lipidomics Facilities at Babraham Institute for technical support; and Cindy Voisine, Michael Witting, Jon Houseley, Len Stephens, Carmen Nussbaum Krammer, Rebeca Aldunate, Patricija van Oosten-Hawle, Jean-Louis Bessereau, and Jane Alfred for feedback on the manuscript. We thank Andy Dillin, Atsushi Kuhara, Amy Walker, Andrew Leifer, Yun Zhang, and Michalis Barkoulas for reagents and Julie Ahringer, Anne Ferguson-Smith, and Anne Corcoran for support and helpful discussions. We also acknowledge Babraham Institute Facilities.
Chauve L, Hodge F, Murdoch S, et al. Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans. PLoS Biology. 2021;19(11). doi:10.1371/journal.pbio.3001431
Chauve, L., Hodge, F., Murdoch, S., Masoudzadeh, F., Mann, H. J., Lopez-Clavijo, A., … Casanueva, O. (2021). Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans. PLoS Biology. Public Library of Science. https://doi.org/10.1371/journal.pbio.3001431
Chauve, Laetitia, Francesca Hodge, Sharlene Murdoch, Fatemah Masoudzadeh, Harry Jack Mann, Andrea Lopez-Clavijo, Hanneke Okkenhaug, et al. “Neuronal HSF-1 Coordinates the Propagation of Fat Desaturation across Tissues to Enable Adaptation to High Temperatures in C. Elegans.” PLoS Biology. Public Library of Science, 2021. https://doi.org/10.1371/journal.pbio.3001431.
L. Chauve et al., “Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans,” PLoS Biology, vol. 19, no. 11. Public Library of Science, 2021.
Chauve L, Hodge F, Murdoch S, Masoudzadeh F, Mann HJ, Lopez-Clavijo A, Okkenhaug H, West G, Sousa BC, Segonds-Pichon A, Li C, Wingett S, Kienberger H, Kleigrewe K, de Bono M, Wakelam M, Casanueva O. 2021. Neuronal HSF-1 coordinates the propagation of fat desaturation across tissues to enable adaptation to high temperatures in C. elegans. PLoS Biology. 19(11), e3001431.
Chauve, Laetitia, et al. “Neuronal HSF-1 Coordinates the Propagation of Fat Desaturation across Tissues to Enable Adaptation to High Temperatures in C. Elegans.” PLoS Biology, vol. 19, no. 11, e3001431, Public Library of Science, 2021, doi:10.1371/journal.pbio.3001431.
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