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

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 deat...

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Autores principales:	James F Clark, Emma J Ciccarelli, Peter Kayastha, Gehan Ranepura, Katerina K Yamamoto, Muhammad S Hasan, Uday Madaan, Alicia Meléndez, Cathy Savage-Dunn
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/e57bf3c063044b4a904d269d7fd7fa6e
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spelling	oai:doaj.org-article:e57bf3c063044b4a904d269d7fd7fa6e2021-12-02T20:03:32ZBMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.1553-73901553-740410.1371/journal.pgen.1009836https://doaj.org/article/e57bf3c063044b4a904d269d7fd7fa6e2021-10-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009836https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404A 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.James F ClarkEmma J CiccarelliPeter KayasthaGehan RanepuraKaterina K YamamotoMuhammad S HasanUday MadaanAlicia MeléndezCathy Savage-DunnPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 10, p e1009836 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 James F Clark Emma J Ciccarelli Peter Kayastha Gehan Ranepura Katerina K Yamamoto Muhammad S Hasan Uday Madaan Alicia Meléndez Cathy Savage-Dunn BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.
description	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.
format	article
author	James F Clark Emma J Ciccarelli Peter Kayastha Gehan Ranepura Katerina K Yamamoto Muhammad S Hasan Uday Madaan Alicia Meléndez Cathy Savage-Dunn
author_facet	James F Clark Emma J Ciccarelli Peter Kayastha Gehan Ranepura Katerina K Yamamoto Muhammad S Hasan Uday Madaan Alicia Meléndez Cathy Savage-Dunn
author_sort	James F Clark
title	BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.
title_short	BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.
title_full	BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.
title_fullStr	BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.
title_full_unstemmed	BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.
title_sort	bmp pathway regulation of insulin signaling components promotes lipid storage in caenorhabditis elegans.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/e57bf3c063044b4a904d269d7fd7fa6e
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BMP pathway regulation of insulin signaling components promotes lipid storage in Caenorhabditis elegans.

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