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 PMID:34634043  

BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.

James F Clark | Emma J Ciccarelli | Peter Kayastha | Gehan Ranepura | Katerina K Yamamoto | Muhammad S Hasan | Uday Madaan | Alicia Meléndez | Cathy Savage-Dunn
PLoS genetics | 2021

A small number of peptide growth factor ligands are used repeatedly in development and homeostasis to drive programs of cell differentiation and function. Cells and tissues must integrate inputs from these diverse signals correctly, while failure to do so leads to pathology, reduced fitness, or death. Previous work using the nematode C. elegans identified an interaction between the bone morphogenetic protein (BMP) and insulin/IGF-1-like signaling (IIS) pathways in the regulation of lipid homeostasis. The molecular components required for this interaction, however, were not fully understood. Here we report that INS-4, one of 40 insulin-like peptides (ILPs), is regulated by BMP signaling to modulate fat accumulation. Furthermore, we find that the IIS transcription factor DAF-16/FoxO, but not SKN-1/Nrf, acts downstream of BMP signaling in lipid homeostasis. Interestingly, BMP activity alters sensitivity of these two transcription factors to IIS-promoted cytoplasmic retention in opposite ways. Finally, we probe the extent of BMP and IIS interactions by testing additional IIS functions including dauer formation, aging, and autophagy induction. Coupled with our previous work and that of other groups, we conclude that BMP and IIS pathways have at least three modes of interaction: independent, epistatic, and antagonistic. The molecular interactions we identify provide new insight into mechanisms of signaling crosstalk and potential therapeutic targets for IIS-related pathologies such as diabetes and metabolic syndrome.

Pubmed ID: 34634043

Research resources used in this publication

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: R15 GM102846
  • Agency: NIGMS NIH HHS, United States
    Id: R15 GM112147

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AxioVision Imaging System (tool)

RRID:SCR_002677

Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376

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Dryad Digital Repository (tool)

RRID:SCR_005910

International, curated, digital repository that makes the data underlying scientific publications discoverable, freely reusable, and citable. Particularly data for which no specialized repository exists. Provides the infrastructure for, and promotes the re-use of, data underlying the scholarly literature. Governed by a nonprofit membership organization. Membership is open to any stakeholder organization, including but not limited to journals, scientific societies, publishers, research institutions, libraries, and funding organizations. Most data are associated with peer-reviewed articles, although data associated with non-peer reviewed publications from reputable academic sources, such as dissertations, are also accepted. Used to validate published findings, explore new analysis methodologies, repurpose data for research questions unanticipated by the original authors, and perform synthetic studies.UC system is member organization of Dryad general subject data repository.

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National Institute of General Medical Sciences (tool)

RRID:SCR_012887

NIGMS supports basic biomedical research that is not targeted to specific diseases. NIGMS funds studies on genes, proteins, and cells, as well as on fundamental processes like communication within and between cells, how our bodies use energy, and how we respond to medicines. The results of this research increase our understanding of life and lay the foundation for advances in disease diagnosis, treatment, and prevention. NIGMS also supports research training programs that produce the next generation of biomedical scientists, and it has special programs to encourage underrepresented minorities to pursue biomedical research careers. The National Institute of General Medical Sciences (NIGMS) primarily supports research that lays the foundation for advances in disease diagnosis, treatment, and prevention. The Institute's research training programs help provide the next generation of scientists. Each year, NIGMS-supported scientists make many advances in understanding fundamental life processes. In the course of answering basic research questions, these investigators increase our knowledge about the mechanisms and pathways involved in certain diseases. Institute grantees also develop important new tools and techniques, some of which have medical applications. In recognition of the significance of their work, a number of NIGMS grantees have received the Nobel Prize and other high scientific honors. At any given time, NIGMS supports approximately 4,700 research grants—approximately 11 percent of the grants funded by NIH as a whole. NIGMS also supports approximately 26 percent of the trainees who receive assistance from NIH. NIGMS also supports approximately 25% of the trainees who receive assistance from NIH. The Institute places great emphasis on supporting investigator-initiated research grants. It funds a limited number of research center grants in selected fields, including structural genomics, trauma and burn research, and systems biology. In addition, NIGMS supports several important scientific resources, including the NIGMS Human Genetic Cell Repository and the Protein Data Bank.

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