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

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=========
Abstracts
=========


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 [[log in to unmask]]
--------------------------------------------------------------------------------


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 [[log in to unmask]]
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[End dictyNews, volume 34, number 4]