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Electronic Edition

Volume 50, number 2

February 9, 2024



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Abstracts

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Darija Putar1, Anja Čizmar1, Xiaoting Chao2,3, Marija Šimić1, Marko 

Šoštar1,Tamara Cutić1, Lucija Mijanović1, Ana Smolko1, Hui Tu2,3, 

Pierre Cosson4, Igor Weber1, Huaqing Cai2,3 and Vedrana Filić1



1 Division of Molecular Biology, Ruđer BoškovićInstitute, Bijenička 

cesta 54, 10000 Zagreb, Croatia,

2 National Laboratory of Biomacromolecules, Institute of Biophysics, 

Chinese Academy of Sciences, 100101 Beijing, People’s Republic 

of China

3 College of Life Sciences, University of Chinese Academy of 

Sciences, 100049 Beijing, People’s Republic of China

4 Department of Cell Physiology and Metabolism, Faculty of 

Medicine, University of Geneva, Geneva, Switzerland





Open Biology 14: 230372, published

https://royalsocietypublishing.org/doi/10.1098/rsob.230372



RasG is a major regulator of macropinocytosis in Dictyostelium 

discoideum. Its activity is under the control of an IQGAP-related 

protein, IqgC, which acts as a RasG-specific GAP (GTPase activating 

protein). IqgC colocalizes with the active Ras at the macropinosome 

membrane during its formation and for some time after the cup closure. 

However, the loss of IqgC induces only a minor enhancement of fluid 

uptake in axenic cells that already lack another RasGAP, NF1. Here, 

we show that IqgC plays an important role in the regulation of 

macropinocytosis in the presence of NF1 byrestricting the size of 

macropinosomes. We further provide evidence that interaction with 

RasG is indispensable for the recruitment of IqgC to forming 

macropinocytic cups. We also demonstrate that IqgC interacts with 

another small GTPase from the Ras superfamily, Rab5A, but is not a 

GAP for Rab5A. Since mammalian Rab5 plays a key role in early endosome 

maturation, we hypothesized that IqgC could be involved in 

macropinosome maturation via its interaction with Rab5A. Although an 

excessive amount of Rab5A reduces the RasGAP activity of IqgC in 

vitro and correlates with IqgC dissociation from endosomes in vivo, 

the physiological significance of the Rab5A–IqgC interaction remains 

elusive.





Submitted by Darija Putar [[log in to unmask]

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Dictyostelium Differentiation-Inducing Factor 1 Promotes

Glucose Uptake via Direct Inhibition of Mitochondrial Malate 

Dehydrogenase in Mouse 3T3-L1 Cells.



Yuzuru Kubohara 1,*, Yuko Fukunaga 2, Ayako Shigenaga 3 and 

Haruhisa Kikuchi 4



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

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

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

Management, Chiba Institute of Science, Choshi 288-0025, Japan

3 Institute of Health and Sports Science & Medicine, Juntendo 

University, Inzai 270-1695, Japan

4 Division of Natural Medicines, Faculty of Pharmacy, Keio 

University, Tokyo 105-8512, Japan





Published in Int. J. Mol. Sci.

https://www.mdpi.com/1422-0067/25/3/1889



Differentiation-inducing factor 1 (DIF-1), found in Dictyostelium 

discoideum, has antiproliferative and glucose-uptake-promoting 

activities in mammalian cells. DIF-1 is a potential lead for the 

development of antitumor and/or antiobesity/antidiabetes drugs, but 

the mechanisms underlying its actions have not been fully elucidated. 

In this study, we searched for target molecules of DIF-1 that mediate 

the actions of DIF-1 in mammalian cells by identifying DIF-1-binding 

proteins in human cervical cancer HeLa cells and mouse 3T3-L1 

fibroblast cells using affinity chromatography and liquid 

chromatography–tandem mass spectrometry and found mitochondrial 

malate dehydrogenase (MDH2) to be a DIF-1-binding protein in both cell 

lines. Since DIF-1 has been shown to directly inhibit MDH2 activity, 

we compared the effects of DIF-1 and the MDH2 inhibitor LW6 on the 

growth of HeLa and 3T3-L1 cells and on glucose uptake in confluent 

3T3-L1 cells in vitro. In both HeLa and 3T3-L1 cells, DIF-1 at 10–40 

microM dose-dependently suppressed growth, whereas LW6 at 20 microM, 

but not at 2–10 microM, significantly suppressed growth in these cells. 

In confluent 3T3-L1 cells, DIF-1 at 10–40 microM significantly promoted 

glucose uptake, with the strongest effect at 20 microM DIF-1, whereas 

LW6 at 2–20 microM significantly promoted glucose uptake, with the 

strongest effect at 10 microM LW6. Western blot analyses showed that 

LW6 (10 microM) and DIF-1 (20 microM) phosphorylated and, thus, 

activated AMP kinase in 3T3-L1 cells. Our results suggest that MDH2 

inhibition can suppress cell growth and promote glucose uptake in the 

cells, but appears to promote glucose uptake more strongly than it 

suppresses cell growth. Thus, DIF-1 may promote glucose uptake, at 

least in part, via direct inhibition of MDH2 and a subsequent 

activation of AMP kinase in 3T3-L1 cells.





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

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[End dictyNews, volume 50, number 2]