dictyNews Electronic Edition Volume 33, number 1 July 3, 2009 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 ========= Histone deacetylases regulate multicellular development in the social amoeba Dictyostelium discoideum. Ritwick Sawarkar, Sandhya S Visweswariah, Wolfgang Nellen and Vidyanand Nanjundiah Journal of Molecular Biology, in press Histone modification is believed to be important for the coordinated regulation of developmental pathways. We have studied the roles of histone deacetylases (HDACs) in the life cycle of Dictyostelium discoideum (Ax2). Our findings are as follows. (1) Bioinformatic analysis shows that there are four putative HDACs in D. discoideum, two each of class I and class II HDACs. A sequence dendrogram of HDAC domains suggests that the two  classII HDACs (HdaC and HdaD) belong to a subgroup of TSA-insensitive  HDACs along with Hos3 of Saccharomyces cerevisiae. (2) One of the four HDAC-encoding genes, hdaA, could not be knocked out, probably because  the gene is essential for growth. However, a strain lacking hdaB could be obtained. hdaB is dispensable for growth and development under laboratory conditions but is required in a social context: cells that lack hdaB function  develop normally but sporulate less efficiently than the wild type in chimeras.  (3) Vegetative cells exhibit HDAC activity in both the nucleus and cytosol.  Nuclear activity is completely inhibited by trichostatin A (TSA), a specific  inhibitor of non-sirtuin HDACs. On the other hand, cytosolic activity is  resistant to TSA. This suggests that the TSA-insensitive class II HDACs  function in the cytosol whereas the class I enzymes are primarily found in  the nucleus. (4) Incubation of growing cells with up to 1 micromolar TSA  causes a moderate increase in histone acetylation without any effect on  generation time. (5) When starving cells are treated with 500 nanomolar  TSA, there is a significant increase in histone acetylation and a delay of  about 3-4 hours in development till the mound stage. Differentiation too is  delayed in TSA-treated cells but cell type proportions are normal.  (6) TSA-treated cells show robust cyclic AMP oscillations comparable to  control cells but the temporal expression profile of some ‘developmental'  genes is affected. In particular, a subset of genes regulated by cAMP and  protein kinase A is delayed. These are the genes encoding the cell  adhesion molecule contact site A (csaA), and calcium binding proteins  (cbpF and cbpA). We infer that HDAC activity influences heterochrony, the relative timing of developmental events, as well as aspects of the phenotype that mediate social behaviour in genetically heterogeneous groups. Submitted by: Vidyanand Nanjundiah [vidya@ces.iisc.ernet.in] -------------------------------------------------------------------------------- Nanovesicles released by Dictyostelium cells : A potential carrier for  drug delivery     Françoise Laviallea, Sophie Deshayesa, Florence Gonnetb, Eric Larquetc,  Sergei G. Kruglika, Nicolas Boissetc§, Regis Danielb, Annette Alfsend,  Irène Tatischeff a*    a CNRS, UMR7033, Université Pierre et Marie Curie, Laboratoire de Biophysique  Moléculaire Cellulaire et Tissulaire, Genopole, F-91030 Evry, France b CNRS, UMR8587, Université Evry val d'Essonne, Laboratoire Analyse et  Modélisation pour la Biologie et l'Environnement, F-91025 Evry, France c CNRS, UMR7590, Institut de Mineralogie et de Physique des Milieux  Condensés, Université Pierre et Marie Curie, F-75252 Paris, France d CNRS, UMR8104, INSERM, U567, Institut Cochin, Département de Biologie  Cellulaire, Université Paris-Descartes, F-75014 Paris, France § Nicolas Boisset deceased on January 2008. *Corresponding author International Journal of Pharmaceutics, in press Nanovesicles released by Dictyostelium discoideum cells grown in the  presence of the DNA-specific dye Hoechst 33342 have been previously  shown to mediate the transfer of the dye into the nuclei of Hoechst-resistant  cells. The present investigation extends this work by conducting experiments  in the presence of hypericin,a fluorescent therapeutic photosensitizer assayed  for antitumoral photodynamic therapy. Nanovesicles released by Dictyostelium  cells exhibit an averaged diameter between 50 and 150 nm, as measured by  transmission cryoelectron microscopy. A proteomic analysis reveals a  predominance of actin and actin-related proteins. The detection of a  lysosomal membrane protein (LIMP II) indicates that these vesicles are  likely generated in the late endosomal compartment. The use of the hypericin- containing nanovesicles as nanodevices for in vitro drug delivery was  investigated by fluorescence microscopy. The observed signal was almost  exclusively located in the perinuclear area of two human cell lines, skin  fibroblasts (HS68) and cervix carcinoma (HeLa) cells. Studies by confocal  microscopy with specific markers of cell organelles, provided evidence that  hypericin was accumulated in the Golgi apparatus. All these data shed a new  light on in vitro drug delivery by using cell-released vesicles as carriers. Submitted by: Irène Tatischeff [irene.tatischeff@upmc.fr] ============================================================== [End dictyNews, volume 33, number 1]