dictyNews

Electronic Edition

Volume 49, number 31

December 9, 2023



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Abstracts

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Pharmacological evidence that Dictyostelium differentiation-inducing 

factor 1 promotes glucose uptake partly via an increase in 

intracellular cAMP content in mouse 3T3-L1 cells.



Yuzuru Kubohara 1,*, Yuko Fukunaga 2, Haruhisa Kikuchi 3, 

Hidekazu Kuwayama 4



1 Laboratory of Health and Life Science, Graduate School of Health 

and Sports Science, Juntendo University, Inzai, Chiba 270-1695, 

Japan; [log in to unmask]

2 Department of Animal Risk Management, Faculty of Risk and Crisis 

Management, Chiba Institute of Sci-ence, Choshi, Chiba 288-0025, 

Japan; [log in to unmask]

3 Division of Natural Medicines, Faculty of Pharmacy, Keio 

University, Tokyo 105-8512, Japan; [log in to unmask]

4 Graduate School of Life and Environmental Sciences, University of 

Tsukuba, Tsukuba, Ibaraki 305-8572, Ja-pan; 

[log in to unmask]





published in Molecules



Differentiation-inducing factor 1 (DIF-1) isolated from the cellular 

slime mold Dictyostelium discoideum can inhibit mammalian calmodulin-

dependent cAMP/cGMP phosphodiesterase (PDE1) in vitro. DIF-1 also 

promotes glucose uptake, at least in part, via a mitochondria- and 

AMPK-dependent pathway in mouse 3T3-L1 fibroblast cells, but the 

mechanism underlying this effect has not been fully elucidated. In 

this study, we investigated the effects of DIF-1 on intracellular 

cAMP and cGMP levels, as well as the effects that DIF-1 and several 

compounds that increase cAMP and cGMP levels have on glucose uptake 

in confluent 3T3-L1 cells. DIF-1 at 20 microM (concentration that 

promotes glucose uptake) increased the level of intracellular cAMP 

by about 20% but did not affect the level of intracellular cGMP. 

Neither the PDE1 inhibitor 8-methoxymethyl-3-isobutyl-1-methylxanthine 

at 10–200 microM nor the broad-range PDE inhibitor 

3-isobutyl-1-methylxanthine at 40–400 microM had any marked effects 

on glucose uptake. The membrane-permeable cAMP analog 8-bromo-cAMP 

at 200–1000 microM significantly promoted glucose uptake (by 20%–25%), 

whereas the membrane-permeable cGMP analog 8-bromo-cGMP at 3–100 

microM did not affect glucose uptake. The adenylate cyclase activator 

forskolin at 1–10 microM promoted glucose uptake by 20%–30%. Thus, 

DIF-1 may promote glucose uptake by 3T3-L1 cells, at least in part, 

via an increase in intracellular cAMP level.





Submitted by Yuzuru Kubohara [[log in to unmask]]

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Functional prokaryotic-like dCTP deaminases and thymidylate synthase 

in eukaryotic social amoebae: vertical, endosymbiotic or horizontal 

gene transfer?



Heng Liang1, Jeffrey P. Mower 2and Catherine P. Chia1 

(corresponding author)



1School of Biological Sciences

2Dept. of Agronomy and Horticulture

Univ. Nebraska-Lincoln





Molecular Biology ad Evolution, Accepted

DOI: 10.1093/molbev/msad268



The de novo synthesis of dTTP uses several pathways: gram-negative 

bacteria use dCTP deaminase (Dcd) to convert dCTP into dUTP, whereas 

eukaryotes and gram-positive bacteria instead use dCMP deaminase to 

transform dCMP to dUMP. It is then unusual that in addition to dCMP 

deaminases, the eukaryote Dictyostelium discoideum has two dCTP 

deaminases (Dcd1Dicty and Dcd2Dicty). Expression of either DcdDicty 

can fully rescue the slow growth of an E. coli dcd knockout. Both 

DcdDicty mitigate the hydroxyurea sensitivity of a 

Schizosaccharomyces pombe dCMP deaminase knockout. Phylogenies show 

that Dcd1Dicty homologs may have entered the common ancestor of the 

eukaryotic groups of Amoebozoa, Obazoa, Metamonada, and Discoba 

through an ancient horizontal gene transfer (HGT) from a prokaryote, 

or an ancient endosymbiotic gene transfer (EGT) from a mitochondrion, 

followed by HGT from Amoebozoa to several other unrelated groups of 

eukaryotes. In contrast, the Dcd2Dicty homologs were a separate HGT 

from a prokaryote, or a virus into either Amoebozoa or Rhizaria, 

followed by an HGT between them. ThyXDicty, the D. discoideum 

thymidylate synthase (TS), another enzyme of the dTTP biosynthesis 

pathway, was suggested previously to be acquired from the ancestral 

mitochondria or by HGT from alpha-proteobacteria. ThyXDicty can 

fully rescue the E. coli TS knockout, and we establish that it 

was obtained by the common ancestor of social amoebae not from 

mitochondria but from a bacterium. We propose HGT and EGT 

contributed to the enzyme diversity of the dTTP synthesis pathway 

in most social amoebae, many Amoebozoa, and other eukaryotes.





Submitted by: Catherine Chia [[log in to unmask]]

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[End dictyNews, volume 49, number 31]