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dictyNews Volume 33 Number 01
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.
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Abstracts
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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]
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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]
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[End dictyNews, volume 33, number 1]
