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
Public Deposited- Creator
-
Torzone S.K.
- Affiliation: College of Arts and Sciences, Department of Biology
-
Park A.Y.
- Affiliation: School of Medicine, Integrative Program for Biological and Genome Sciences
-
Breen P.C.
- Affiliation: School of Medicine, Integrative Program for Biological and Genome Sciences
-
Cohen N.R.
- Affiliation: School of Medicine, Integrative Program for Biological and Genome Sciences
-
Dowen R.H.
- Affiliation: College of Arts and Sciences, Department of Biology
- Abstract
- AAUnim: Pallseainsetecgonrafitremdtheavteallolhpemadeinntgalleavenldsanruertreiptiroensaenl tseidgcnoarlrsebctelyfo: re 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.
- Date of publication
- 2023
- Keyword
- protein analysis
- gene
- synaptophysin
- oil red o staining
- Animals
- Hormones
- staining
- CRISPR-CAS9 system
- fluorescence intensity
- lifespan
- Lipids
- glycoprotein
- G protein coupled receptor
- coimmunoprecipitation
- transgenic animal
- real time polymerase chain reaction
- MAPK signaling
- follitropin
- metabolism
- gene editing
- lipid
- Caenorhabditis elegans protein
- Glycoproteins
- RNA isolation
- Escherichia coli
- animal
- homeostasis
- RNA interference
- mitogen activated protein kinase p38
- oligomerization
- hormone
- FLR 2
- autofluorescence
- Caenorhabditis elegans Proteins
- genetics
- growth rate
- mammal
- Mammals
- Western blotting
- growth
- unclassified drug
- imaging
- ultrasound
- nonhuman
- mitogen activated protein kinase
- brood size
- Caenorhabditis elegans
- lipid homeostasis
- body size
- polyacrylamide gel electrophoresis
- p38 Mitogen-Activated Protein Kinases
- Homeostasis
- Article
- cyclic AMP dependent protein kinase
- whole genome sequencing
- DRL-1/FLR-4 gene
- DOI
- Identifier
- Resource type
- Article
- License
- Attribution 4.0 International
- Journal title
- PLoS Biology
- Journal volume
- 21
- Journal issue
- 9
- Language
- English
- Version
- Publisher
- ISSN
- 1544-9173
- Publisher
- Public Library of Science
Relations
- Parents:
- In Collection:
This work has no parents.
Items
| Thumbnail | Title | Date Uploaded | Visibility | Actions |
|---|---|---|---|---|
|
|
journal.pbio.3002320.pdf | 2023-11-06 | Public | Download |