Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism

mTORC1 and AMPK are mutually antagonistic sensors of nutrient and energy status that have been implicated in many human diseases including cancer, Alzheimer’s disease, obesity and type 2 diabetes. Starved cells of the social amoeba Dictyostelium discoideum aggregate and eventually form fruiting bodi...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Julian D. Gross, Catherine J. Pears
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Dictyostelium discoideum cell fate decision AMP-dependent protein kinase (AMPK) mechanistic target of rapamycin complex 1 (mTORC1) ammonia acidic vesicles Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/1c581b558f814ea6bb852af8ae9181dd
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:1c581b558f814ea6bb852af8ae9181dd
record_format	dspace
spelling	oai:doaj.org-article:1c581b558f814ea6bb852af8ae9181dd2021-11-08T05:00:55ZPossible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism2296-634X10.3389/fcell.2021.758317https://doaj.org/article/1c581b558f814ea6bb852af8ae9181dd2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.758317/fullhttps://doaj.org/toc/2296-634XmTORC1 and AMPK are mutually antagonistic sensors of nutrient and energy status that have been implicated in many human diseases including cancer, Alzheimer’s disease, obesity and type 2 diabetes. Starved cells of the social amoeba Dictyostelium discoideum aggregate and eventually form fruiting bodies consisting of stalk cells and spores. We focus on how this bifurcation of cell fate is achieved. During growth mTORC1 is highly active and AMPK relatively inactive. Upon starvation, AMPK is activated and mTORC1 inhibited; cell division is arrested and autophagy induced. After aggregation, a minority of the cells (prestalk cells) continue to express much the same set of developmental genes as during aggregation, but the majority (prespore cells) switch to the prespore program. We describe evidence suggesting that overexpressing AMPK increases the proportion of prestalk cells, as does inhibiting mTORC1. Furthermore, stimulating the acidification of intracellular acidic compartments likewise increases the proportion of prestalk cells, while inhibiting acidification favors the spore pathway. We conclude that the choice between the prestalk and the prespore pathways of cell differentiation may depend on the relative strength of the activities of AMPK and mTORC1, and that these may be controlled by the acidity of intracellular acidic compartments/lysosomes (pHv), cells with low pHv compartments having high AMPK activity/low mTORC1 activity, and those with high pHv compartments having high mTORC1/low AMPK activity. Increased insight into the regulation and downstream consequences of this switch should increase our understanding of its potential role in human diseases, and indicate possible therapeutic interventions.Julian D. GrossCatherine J. PearsFrontiers Media S.A.articleDictyostelium discoideumcell fate decisionAMP-dependent protein kinase (AMPK)mechanistic target of rapamycin complex 1 (mTORC1)ammoniaacidic vesiclesBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Dictyostelium discoideum cell fate decision AMP-dependent protein kinase (AMPK) mechanistic target of rapamycin complex 1 (mTORC1) ammonia acidic vesicles Biology (General) QH301-705.5
spellingShingle	Dictyostelium discoideum cell fate decision AMP-dependent protein kinase (AMPK) mechanistic target of rapamycin complex 1 (mTORC1) ammonia acidic vesicles Biology (General) QH301-705.5 Julian D. Gross Catherine J. Pears Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism
description	mTORC1 and AMPK are mutually antagonistic sensors of nutrient and energy status that have been implicated in many human diseases including cancer, Alzheimer’s disease, obesity and type 2 diabetes. Starved cells of the social amoeba Dictyostelium discoideum aggregate and eventually form fruiting bodies consisting of stalk cells and spores. We focus on how this bifurcation of cell fate is achieved. During growth mTORC1 is highly active and AMPK relatively inactive. Upon starvation, AMPK is activated and mTORC1 inhibited; cell division is arrested and autophagy induced. After aggregation, a minority of the cells (prestalk cells) continue to express much the same set of developmental genes as during aggregation, but the majority (prespore cells) switch to the prespore program. We describe evidence suggesting that overexpressing AMPK increases the proportion of prestalk cells, as does inhibiting mTORC1. Furthermore, stimulating the acidification of intracellular acidic compartments likewise increases the proportion of prestalk cells, while inhibiting acidification favors the spore pathway. We conclude that the choice between the prestalk and the prespore pathways of cell differentiation may depend on the relative strength of the activities of AMPK and mTORC1, and that these may be controlled by the acidity of intracellular acidic compartments/lysosomes (pHv), cells with low pHv compartments having high AMPK activity/low mTORC1 activity, and those with high pHv compartments having high mTORC1/low AMPK activity. Increased insight into the regulation and downstream consequences of this switch should increase our understanding of its potential role in human diseases, and indicate possible therapeutic interventions.
format	article
author	Julian D. Gross Catherine J. Pears
author_facet	Julian D. Gross Catherine J. Pears
author_sort	Julian D. Gross
title	Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism
title_short	Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism
title_full	Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism
title_fullStr	Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism
title_full_unstemmed	Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism
title_sort	possible involvement of the nutrient and energy sensors mtorc1 and ampk in cell fate diversification in a non-metazoan organism
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1c581b558f814ea6bb852af8ae9181dd
work_keys_str_mv	AT juliandgross possibleinvolvementofthenutrientandenergysensorsmtorc1andampkincellfatediversificationinanonmetazoanorganism AT catherinejpears possibleinvolvementofthenutrientandenergysensorsmtorc1andampkincellfatediversificationinanonmetazoanorganism
_version_	1718442978921414656

Possible Involvement of the Nutrient and Energy Sensors mTORC1 and AMPK in Cell Fate Diversification in a Non-Metazoan Organism

Ejemplares similares