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- W4387164893 endingPage "e3002320" @default.
- W4387164893 startingPage "e3002320" @default.
- W4387164893 abstract "Animals integrate developmental and nutritional signals before committing crucial resources to growth and reproduction; however, the pathways that perceive and respond to these inputs remain poorly understood. Here, we demonstrate that DRL-1 and FLR-4, which share similarity with mammalian mitogen-activated protein kinases, maintain lipid homeostasis in the C . elegans intestine. DRL-1 and FLR-4 function in a protein complex at the plasma membrane to promote development, as mutations in drl-1 or flr-4 confer slow growth, small body size, and impaired lipid homeostasis. To identify factors that oppose DRL-1/FLR-4, we performed a forward genetic screen for suppressors of the drl-1 mutant phenotypes and identified mutations in flr-2 and fshr-1 , which encode the orthologues of follicle stimulating hormone and its putative G protein–coupled receptor, respectively. In the absence of DRL-1/FLR-4, neuronal FLR-2 acts through intestinal FSHR-1 and protein kinase A signaling to restrict growth. Furthermore, we show that opposing signaling through DRL-1 and FLR-2 coordinates TIR-1 oligomerization, which modulates downstream p38/PMK-1 activity, lipid homeostasis, and development. Finally, we identify a surprising noncanonical role for the developmental transcription factor PHA-4/FOXA in the intestine where it restricts growth in response to impaired DRL-1 signaling. Our work uncovers a complex multi-tissue signaling network that converges on p38 signaling to maintain homeostasis during development." @default.
- W4387164893 created "2023-09-30" @default.
- W4387164893 creator A5010980940 @default.
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- W4387164893 creator A5085637267 @default.
- W4387164893 date "2023-09-29" @default.
- W4387164893 modified "2023-10-14" @default.
- W4387164893 title "Opposing action of the FLR-2 glycoprotein hormone and DRL-1/FLR-4 MAP kinases balance p38-mediated growth and lipid homeostasis in C. elegans" @default.
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- W4387164893 doi "https://doi.org/10.1371/journal.pbio.3002320" @default.
- W4387164893 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37773960" @default.
- W4387164893 hasPublicationYear "2023" @default.
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