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dictyNews Volume 22 Number 02
Dicty News
Electronic Edition
Volume 22, number 2
January 30, 2004
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 Dicty-News, the Dicty Reference database and other
useful information is available at dictyBase - http://dictybase.org.
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Abstracts
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Developmental cell death in Dictyostelium does not require paracaspase.
Roisin-Bouffay C, Luciani MF, Klein G, Levraud JP, Adam M, Golstein P.
Centre d'Immunologie de Marseille-Luminy, INSERM-CNRS-Univ.Med., 13288
Marseille cedex 9.
J Biol Chem. 2003 Dec 17 [Epub ahead of print], 2004 in press
Apoptotic cell death often requires caspases. Caspases are part of a family
of related molecules including also paracaspases and metacaspases. Are
molecules of this family generally involved in cell death ? More
specifically, do non-apoptotic caspase-independent types of cell death
require para- or metacaspases ? Dictyostelium discoideum lends itself well
to answering these questions, since (1) it undergoes non-apoptotic
developmental cell death, of a vacuolar autophagic type, and (2) it bears
neither caspase nor metacaspase genes and apparently only one paracaspase
gene. This only paracaspase gene can be inactivated by homologous
recombination. Paracaspase-null clones were thus obtained in each of four
distinct Dictyostelium strains. These clones were tested in two systems,
developmental stalk cell death in vivo and vacuolar autophagic cell death
in a monolayer system mimicking developmental cell death. Compared to
parent cells, all paracaspase-null cells showed unaltered cell death, in
both test systems. In addition, paracaspase inactivation led to no
alteration in development or interaction with a range of bacteria. Thus,
in Dictyostelium, vacuolar programmed cell death in development and in a
monolayer model in vitro would seem not to require paracaspase. To our
knowledge, this is the first instance of developmental, programmed cell
death shown to be independent of any caspase, para- or metacaspase. These
results have implications as to the relationship in evolution between cell
death and the caspase family.
Submitted by: Pierre Golstein [golstein@ciml.univ-mrs.fr]
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Molecular engineering of a backwards-moving myosin motor
Georgios Tsiavaliaris, Setsuko Fujita-Becker, & Dietmar J. Manstein
Nature, in press
All members of the diverse myosin superfamily have a highly conserved globular
motor domain that contains the actin and nucleotide binding sites and produces
force and movement. The light chain binding domain connects the motor domain
to a variety of functionally specialized tail domains and amplifies small
structural changes in the core motor domain via rotation of a lever arm.
Myosins move on polarised actin filaments either forwards to the barbed (+)
or backwards to the pointed (-) end. Here, we describe the engineering of an
artificial backwards moving myosin from three pre-existing molecular building
blocks: a forward-moving class I myosin motor domain, a directional inverter
formed by a 4-helix bundle segment of human guanylate binding protein-1, and
an artificial lever arm formed by two a-actinin repeats. Our results prove
that reverse-direction movement of myosins can be achieved simply by rotating
the direction of the lever arm 180¡.
Submitted by: Dietmar Manstein [Manstein.Dietmar@mh-hannover.de]
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Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) is a
pharmacological target of DIF-1, an anti-tumor agent isolated from
Dictyostelium
Kasumi Shimizu, Taku Murata, Toshiro Tagawa, Katsunori Takahashi, Ryoki
Ishikawa, Yumiko Abe, Kohei Hosaka, and Yuzuru Kubohara*
*Biosignal Research Center, Institute for Molecular and Cellular Regulation
(IMCR), Gunma University, Maebashi 371-8512, Japan.
Accepted for publication in Cancer Research
Abstract
The differentiation-inducing factor-1 (DIF-1) isolated from Dictyostelium
discoideum is a potent anti-proliferative agent that induces growth arrest
and differentiation in mammalian cells in vitro. However, the specific
target molecule(s) of DIF-1 has not been identified. In this study, we
have tried to identify the target molecule(s) of DIF-1 in mammalian cells,
examining the effects of DIF-1 and its analogs on the activity of some
candidate enzymes. DIF-1 at 10-40 micro M dose-dependently suppressed cell
growth and increased the intracellular cAMP concentration in K562 leukemia
cells. It was then found that DIF-1 at 0.5-20 micro M inhibited the
calmodulin (CaM)-dependent cyclic nucleotide phosphodiesterase (PDE1) in
vitro in a dose-dependent manner. Kinetic analysis revealed that DIF-1 acted
as a competitive inhibitor of PDE1 versus the substrate cAMP. Since DIF-1
did not significantly affect the activity of other PDEs or CaM-dependent
enzymes and, in addition, an isomer of DIF-1 was a less potent inhibitor,
we have concluded that PDE1 is a pharmacological and specific target of DIF-1.
Submitted by: Yuzuru Kubohara [kubohara@showa.gunma-u.ac.jp]
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[End Dicty News, volume 22, number 2]
