Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity

dc.contributor.authorArneaud, Sonja L.B.
dc.contributor.authorMcClendon, Jacob
dc.contributor.authorTatge, Lexus
dc.contributor.authorWatterson, Abigail
dc.contributor.authorZuurbier, Kielen R.
dc.contributor.authorMadhu, Bhoomi
dc.contributor.authorGumienny, Tina L.
dc.contributor.authorDouglas, Peter M.
dc.descriptionArticle originally published in Aging Cell, 21(9). English. Published online 2023.
dc.description.abstractAging is a complex and highly regulated process of interwoven signaling mechanisms. As an ancient transcriptional regulator of thermal adaptation and protein homeostasis, the Heat Shock Factor, HSF-1, has evolved functions within the nervous system to control age progression; however, the molecular details and signaling dynamics by which HSF-1 modulates age across tissues remain unclear. Herein, we report a nonautonomous mode of age regulation by HSF-1 in the Caenorhabditis elegans nervous system that works through the bone morphogenic protein, BMP, signaling pathway to modulate membrane trafficking in peripheral tissues. In particular, HSF-1 represses the expression of the neuron-specific BMP ligand, DBL-1, and initiates a complementary negative feedback loop within the intestine. By reducing receipt of DBL-1 in the periphery, the SMAD transcriptional coactivator, SMA-3, represses the expression of critical membrane trafficking regulators including Rab GTPases involved in early (RAB-5), late (RAB-7), and recycling (RAB-11.1) endosomal dynamics and the BMP receptor binding protein, SMA-10. This reduces cell surface residency and steady-state levels of the type I BMP receptor, SMA-6, in the intestine and further dampens signal transmission to the periphery. Thus, the ability of HSF-1 to coordinate BMP signaling along the gut–brain axis is an important determinate in age progression.en_US
dc.description.abstractAbbreviations: BMP, Bone morphogenic protein; EV, Empty vector; FUdR, 5-fluorouracil- 2'- deoxyribose; GFP, Green fluorescent protein; HSF, Heat shock factor; LRIG, Leucine rich and immunoglobulin domains; NGM, Nematode growth medium; qPCR, Quantitative reverse-transcriptase PCR; TB, Terrific broth; TGF, Transforming growth factor; WT, wild-type.
dc.description.sponsorshipWe thank Venkat Malladi from the UT Southwestern Bioinformatics Core Facility, funded by the Cancer Prevention and Research Institute of Texas (CPRIT, RP150596), for binding site analysis. We appreciate both the Morimoto and Savage-Dunn lab for making ChIP-seq datasets publicly available. We thank the Caenorhabditis Genetics Center (CGC) and the Dillin, Grant, and Padgett laboratories for strains used in this study. We extend our gratitude to our funding sources: TWU institutional funds to BM and TLG and the American Federation of Aging Research, the Glenn Center for Aging, the Welch Foundation (I-2061-20210327), the NIH (R01AG076529 and R01AG061338 to PMD) and RO1GM097591 to TLG. Schematics created with
dc.identifier.citationThis is a published version of an article that is available at: Recommended citation: Arneaud, S. L., McClendon, J., Tatge, L., Watterson, A., Zuurbier, K. R., Madhu, B., Gumienny, T. L., & Douglas, P. M. (2022). Reduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevity. Aging Cell, 21(9). This item has been deposited in accordance with publisher copyright and licensing terms and with the author’s permission.en_US
dc.rights.holder© 2022 The Authors
dc.rights.licenseCC BY 4.0
dc.subjectBMP signalingen_US
dc.subjectGut–neuron axisen_US
dc.subjectMembrane trafficen_US
dc.subjectRab GTPasesen_US
dc.titleReduced bone morphogenic protein signaling along the gut–neuron axis by heat shock factor promotes longevityen_US


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