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dictyNews Volume 22 Number 09
Dicty News
Electronic Edition
Volume 22, number 9
April 9, 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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Periodic signaling controlled by an oscillatory circuit that includes
protein kinases ERK2 and PKA.
Mineko Maeda, Sijie Lu, Gad Shaulsky, Yuji Miyazaki, Hidekazu Kuwayama,
Yoshimasa Tanaka, Adam Kuspa, and William F. Loomis
Department of Biology, Osaka University, Osaka, Japan; Departments of
Biochemistry and Molecular Biology and Molecular and Human Genetics, Baylor
College of Medicine, Houston TX; Institute of Biological Sciences,
University of Tsukuba, Ibaraki, Japan; Division of Biological Sciences,
University of California San Diego, La Jolla, CA
Science, in press
Self-regulating systems often employ robust oscillatory circuits. One such
system controls the chemotactic signaling mechanism of Dictyostelium where
pulses of cAMP are generated with a 7 minute periodicity. We have observed
spontaneous oscillations in activation of the MAP kinase ERK2 that occur in
phase with peaks of cAMP and show that ERK2 modulates cAMP levels through the
phosphodiesterase RegA. Computer modeling and simulations of the underlying
circuit faithfully account for the ability of the cells to spontaneously
generate periodic pulses during specific stages of development. Similar
oscillatory processes may occur in cells of many different species.
Submitted by: Bill Loomis [wloomis@ucsd.edu]
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A Galpha-Dependent Pathway that Antagonizes Multiple Chemoattractant
Responses that Regulate Directional Cell Movement
Joseph A. Brzostowski *, Carole A. Parent +, and Alan R. Kimmel *
* LCDB, NIDDK, + LCMB, CCR, NCI,
National Institutes of Health, Bethesda, MD 20892-8028
Genes and Development, in press
Chemotactic cells, including neutrophils and Dictyostelium discoideum, orient
and move directionally in very shallow chemical gradients. As cells polarize,
distinct structural and signaling components become spatially constrained to
the leading edge or rear of the cell. It has been suggested that complex
feedback loops that function downstream of receptor signaling integrate
activating and inhibiting pathways to establish cell polarity within such
gradients. Much effort has focused on defining activating pathways, whereas
inhibitory networks have remained largely unexplored. We have identified a
novel signaling function in Dictyostelium involving a Galpha subunit (Galpha9)
that antagonizes broad chemotactic response. Mechanistically, Galpha9
functions rapidly following receptor stimulation to negatively regulate
PI3K/PTEN, adenylyl cyclase, and guanylyl cyclase pathways. The coordinated
activation of these pathways is required to establish the asymmetric
mobilization of actin and myosin that typifies polarity and ultimately directs
chemotaxis. Most dramatically, cells lacking Galpha9 have extended PI(3,4,5)P3,
cAMP, and cGMP responses and are hyperpolarized. In contrast, cells expressing
constitutively activated Galpha9 exhibit a reciprocal phenotype. Their second
message pathways are attenuated, and they have lost the ability to suppress
lateral pseudopod formation. Potentially, functionally similar Galpha-mediated
inhibitory signaling may exist in other eukaryotic cells to regulate
chemoattractant response.
Submitted by: Joseph Brzostowski [jb363a@nih.gov]
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An Orderly Retreat: Dedifferentiation is a Regulated Process
Mariko Katoh 1,4, Chad Shaw 1, Qikai Xu 1,2, Nancy Van Driessche 1,3,
Takahiro Morio 4, Hidekazu Kuwayama 4, Shinji Obara 4, Hideko Urushihara 4,
Yoshimasa Tanaka 4,6 and Gad Shaulsky 1,2,3,5
1 Department of Molecular and Human Genetics, 2Graduate Program in Structural
and Computational Biology and Molecular Biophysics, 3 Graduate Program in
Developmental Biology, Baylor College of Medicine, Houston, TX, USA
4 Institute of Biological Sciences, University of Tsukuba, Tsukuba, Ibaraki,
Japan
PNAS, in press (edited by Igor B. Dawid)
ABSTRACT
Differentiation is a highly regulated process whereby cells become specialized
to perform specific functions and lose the ability to perform others. In
contrast, the question of whether dedifferentiation is a genetically
determined process, or merely an unregulated loss of the differentiated state,
has not been resolved. We show here that dedifferentiation in the social
amoeba Dictyostelium discoideum relies on a sequence of events that is
independent of the original developmental state and involves the coordinated
expression of a specific set of genes. A defect in one of these genes, the
histidine kinase dhkA, alters the kinetics of dedifferentiation and uncouples
the progression of dedifferentiation events. These observations establish
dedifferentiation as a genetically determined process and suggest the existence
of a developmental checkpoint that ensures a return path to the
undifferentiated state.
Submitted by: Gad Shaulsky [gadi@bcm.tmc.edu]
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[End Dicty News, volume 22, number 9]
