dictyNews Electronic Edition Volume 34, number 4 February 5, 2010 Please submit abstracts of your papers as soon as they have been accepted for publication by sending them to dicty@northwestern.edu or by using the form at http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit. Back issues of dictyNews, the Dicty Reference database and other useful information is available at dictyBase - http://dictybase.org. Follow dictyBase on twitter: http://twitter.com/dictybase ========= 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 [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] ============================================================== [End dictyNews, volume 34, number 4]