dictyNews

Electronic Edition

Volume 47, number 22

November 12, 2021



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Abstracts

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Possible Involvement of the Nutrient and Energy Sensors mTORC1 

and AMPK in Cell Fate Diversification in a Non-Metazoan Organism



Julian D. Gross and Catherine J. Pears



Department of Biochemistry, University of Oxford, Oxford,

United Kingdom





Frontiers in Cell and Developmental Biology

doi:10.3389/fcell.2021.758317

 

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.



 

Submitted by Julian Gross [[log in to unmask]]

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A chemorepellent inhibits local Ras activation to inhibit pseudopod 

formation to bias cell movement away from the chemorepellent



Sara A. Kirolos and Richard H. Gomer



Department of Biology, Texas A&M University





MBoC, in press



The ability of cells to sense chemical gradients is essential during 

development, morphogenesis, and immune responses. Although 

much is known about chemoattraction, chemorepulsion remains poorly 

understood. Proliferating Dictyostelium cells secrete a chemorepellent 

protein called AprA. AprA prevents pseudopod formation at the region 

of the cell closest to the source of AprA, causing the random movement 

of cells to be biased away from the AprA. Activation of Ras proteins in 

a localized sector of a cell cortex helps to induce pseudopod formation, 

and Ras proteins are needed for AprA chemorepulsion. Here we show 

that AprA locally inhibits Ras cortical activation through the G protein-

coupled receptor GrlH, the G protein subunits Galpha and Galpha8, 

Ras protein RasG, protein kinase B, the p-21 activated kinase PakD, 

and the extracellular signal-regulated kinase Erk1. Diffusion calculations 

and experiments indicate that in a colony of cells, high extracellular 

concentrations of AprA in the center can globally inhibit Ras activation, 

while a gradient of AprA that naturally forms at the edge of the colony 

allow cells to activate Ras at sectors of the cell other than the sector 

of the cell closest to the center of the colony, effectively inducing both 

repulsion from the colony and cell differentiation. Together, these 

results suggest that a pathway that inhibits local Ras activation can 

mediate chemorepulsion. 





submitted by: Sara Kirolos [[log in to unmask]]

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[End dictyNews, volume 47, number 22]