dictyNews Electronic Edition Volume 27, number 11 October 6, 2006 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. ============= Abstracts ============= Molecular phylogeny and evolution of morphology in the social amoebas 1Pauline Schaap, 2Thomas Winckler, 3Michaela Nelson, 1Elisa Alvarez-Curto, 3Barrie Elgie, 4Hiromitsu Hagiwara, 5James Cavender, 1Alicia Milano-Curto, 1Daniel E. Rozen, 6Theodor Dingermann, 7 Rupert Mutzel and 3Sandra L. Baldauf* Science, in press The social amoebas (Dictyostelia) display conditional multicellularity in a wide variety of forms. Despite widespread interest in Dictyostelium discoideum as a model system, there is almost no molecular data from the rest of the group. We have constructed the first molecular phylogeny of the Dictyostelia with parallel small subunit ribosomal RNA and alpha-tubulin datasets and find that dictyostelid taxonomy requires complete revision. A mapping of characters onto the phylogeny shows that the dominant trend in dictyostelid evolution is increased size and cell-type specialization of fruiting structures, but not architectural complexity. This major taxon is now uniquely well suited to study molecular changes underlying phenotypic innovation. Submitted by: Pauline Schaap [p.schaap@dundee.ac.uk] ----------------------------------------------------------------------------- Pharmacological profiling of the Dictyostelium adenylyl cyclases ACA, ACB and ACG. Elisa Alvarez-Curto, Karin E. Weening and Pauline Schaap Biochemical Journal, in press Intracellular and secreted cAMP play crucial roles in controlling cell movement and gene regulation throughout development of the social amoeba Dictyostelium discoideum. cAMP is produced by three structurally distinct adenylyl cyclases, ACA, ACG and ACB which have distinctive but overlapping patterns of expression and, as concluded from gene disruption studies, seemingly overlapping functions. In addition to gene disruption, acute pharmacological abrogation of protein activity can be a powerful tool to identify its role in the biology of the organism. We analysed the effects of a range of compounds on the activity of ACA, ACB and ACG to identify enzyme-specific modulators. Caffeine, which was previously used to specifically block ACA function, also inhibited cAMP accumulation by ACB and ACG. 2'3'-O-methyl isopropylidene adenosine (IPA) specifically inhibits ACA when measured in intact cells, without affecting ACB or ACG. All three enzymes are inhibited by the P-site inhibitor 2'5'dideoxyadenosine (DDA) when assayed in cell lysates, but not in intact cells. Tyrphostin A25 and SQ22536 proved to be effective and specific inhibitors for ACG and ACA respectively. Both compounds acted directly on enzyme activity assayed in cell lysates, but only SQ22536 was also a specific inhibitor when added to intact cells. Submitted by: Pauline Schaap [p.schaap@dundee.ac.uk] ----------------------------------------------------------------------------- Correction of the abstract that appeared in the dictyNews, v27, #7: Anti-leukemic activities of Dictyostelium secondary metabolites: A novel aromatic metabolite, 4-methyl-5-n-pentylbenzene-1,3-diol, isolated from Dictyostelium mucoroides suppresses cell growth in human leukemia K562 and HL-60 cells. Haruhisa Kikuchi, Yoshiteru Oshima, Aya Ichimura, Naomi Gokan, Aiko Hasegawa, Kohei Hosaka, Yuzuru Kubohara Tohoku University & Gunma University, Japan. Life Sciences, In press It has previously been shown that DIF-1, a differentiation-inducing factor of the cellular slime mold Dictyostelium discoideum, possesses antitumor activities in mammalian tumor cells and that neuronal differentiation of PC12 cells can be induced with furanodictines (FDs), aminosugar analogs found in D. discoideum, or dictyoglucosamines (DGs), N-acetyl glucosamine derivatives (DG-A from D. purpureum and DG-B from D. discoideum). Thus, cellular slime molds are attractive natural resources that may provide valuable lead compounds to be utilized in the field of pharmacology and medicine. In this study, we have isolated a novel aromatic compound, 4-methyl-5-n-pentylbenzene-1,3-diol (MPBD), from fruiting bodies of the cellular slime mold D. mucoroides and assessed the in vitro antiproliferative activities of MPBD, FDs, and DGs in human leukemia K562 and HL-60 cells. MPBD at 20-80 microM dose-dependently suppressed cell growth in both K562 and HL-60 cells. While FDs at 10-80 microM did not affect cell growth, DGs at 10-40 microM dose-dependently suppressed cell growth in the cells. Although we failed to find the roles of FDs and DGs in the original organisms, MPBD at 5-20 microM was found to promote stalk cell formation in D. discoideum. The present results indicate that MPBD, DGs or their derivatives may have therapeutic potential in the treatment of cancer and confirm our expectations regarding cellular slime molds as drug resources. Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp] ============================================================================== [End dictyNews, volume 27, number 11]