dictyNews
Electronic Edition
Volume 34, number 4
February 5, 2010

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=========
Abstracts
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Dictyostelium differentiation-inducing factor-1 binds to mitochondrial malate 
dehydrogenase and inhibits its activity.

Tomoko Matsuda, Fumi Takahashi-Yanaga*, Tatsuya Yoshihara1, Katsumi Maenaka, 
Yutaka Watanabe, Yoshikazu Miwa, Sachio Morimoto, Yuzuru Kubohara, 
Masato Hirata, Toshiyuki Sasaguri

*Correspondence: Department of Clinical Pharmacology, Faculty of Medical Sciences, 
Kyushu University, Fukuoka 812-8582, Japan


J. Pharmacol. Sci., in press

We have reported that the differentiation-inducing factors (DIFs) DIF-1 and DIF-3, 
morphogens secreted from Dictyostelium discoideum, inhibit proliferation of several 
cancer cells via suppressing the Wnt/beta-catenin signaling pathway. However,
the target molecules of DIFs involved in the anti-proliferative effects are still 
unknown. In the present study, DIF-1-tethered resins were synthesized to explore 
the target molecules of DIFs and mitochondrial malate dehydrogenase (mMDH) 
was identified as one of the target molecules. In the in vitro assay, DIF-1 and other 
analogs including 2-MIDIF-1, DIF-3, and 6-MIDIF-3 were found to be capable of 
binding to mMDH but not to cytoplasmic MDH. However, only DIF-1 and 2-MIDIF-1 
inhibited the enzymatic activity of mMDH. The effects of DIF analogs on ATP 
content and cell proliferation were then analyzed using HeLa cells. DIF-1 and 
2-MIDIF-1 were found to lower the ATP content and both chemicals inhibited 
HeLa cell proliferation, suggesting that inhibition of mMDH activity affected cell 
energy production, probably leading to the inhibition of proliferation. These 
results suggest that the inhibition of mMDH activity by DIF-1 and 2-MIDIF-1 
could be one of mechanism to induced anti- proliferative effects, independent 
of the inhibition of the Wnt/beta-catenin signaling pathway.


Submitted by Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp]
--------------------------------------------------------------------------------


Functional roles of VASP phosphorylation in the regulation of chemotaxis and 
osmotic stress response

Wan-Hsin Lin*, Sharon E. Nelson#, Ryan J. Hollingsworth#, Chang Y. Chung#*

Department of Pharmacology#, Vanderbilt University Medical Center, and 
Department of Biological Sciences*, School of Art and Science, 
Vanderbilt University, Nashville, TN 37232-6600


Cytoskeleton, in press

VASP plays crucial roles in controlling F-actin-driven processes and growing 
evidence indicates that VASP function is modulated by phosphorylation at 
multiple sites. However, the complexity of mammalian system prevents the 
clear understanding of the role of VASP phosphorylation. In this study, we 
took advantage of Dictyostelium which possesses only one member of the 
Ena/VASP family to investigate the functional roles of VASP phosphorylation. 
Our results demonstrated that hyperosmotic stress and cAMP stimulation 
cause VASP phosphorylation. VASP phosphorylation plays a negative role 
for the early steps of filopodia/microspikes formation.  VASP phosphorylation 
appears to modulate VASP localization at the membrane cortex and its 
interactions with WASP and WIPa. Analysis of chemotaxis of cells expressing 
VASP mutants showed that VASP phosphorylation is required for the 
establishment of cell polarity under a cAMP gradient.


Submitted by Chang Chung [chang.chung@vanderbilt.edu]
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[End dictyNews, volume 34, number 4]