dictyNews
Electronic Edition
Volume 34, number 19
June 25, 2010
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=========
Abstracts
=========
Self-organization of the phosphatidylinositol lipids signaling system
for
random cell migration
Yoshiyuki Arai, Tatsuo Shibata, Satomi Matsuoka, Masayuki J. Sato,
Toshio Yanagida, and Masahiro Ueda
Graduate School of Frontier Biosciences, Osaka University and JST,
CREST, Suita, Osaka 565-0871, Japan.
Department of Mathematical and Life Sciences, Hiroshima University and
JST, PRESTO, Higashi-Hiroshima, Hiroshima 739-8526, Japan.
Proc. Natl. Acad. Sci. USA , in press.
Phosphatidylinositol (PtdIns) lipids have been identified as key
signaling
mediators for random cell migration as well as chemoattractant-induced
directional migration. However, how the PtdIns lipids are organized
spatiotemporally to regulate cellular motility and polarity remains to
be
clarified. Here, we found that selforganized waves of PtdIns 3,4,5-
trisphosphate
[PtdIns(3,4,5)P3] are generated spontaneously on the membrane of
Dictyostelium cells in the absence of a chemoattractant. Characteristic
oscillatory dynamics within the PtdIns lipids signaling system were
determined
experimentally by observing the phenotypic variability of PtdIns lipid
waves in
single cells, which exhibited characteristics of a relaxation
oscillator. The
enzymes phosphatase and tensin homolog (PTEN) and
phosphoinositide-3-kinase (PI3K), which are regulators for PtdIns lipid
concentrations along the membrane, were essential for wave generation
whereas functional actin cytoskeleton was not. Defects in these enzymes
inhibited wave generation as well as actin-based polarization and cell
migration.
On the basis of these experimental results, we developed a reaction-
diffusion
model that reproduced the characteristic relaxation oscillation
dynamics of the
PtdIns lipid system, illustrating that a self-organization mechanism
provides the
basis for the PtdIns lipids signaling system to generate spontaneous
spatiotemporal signals for random cell migration and that molecular
noise
derived from stochastic fluctuations within the signaling components
gives
rise to the variability of these spontaneous signals.
Submitted by Masahiro Ueda [[log in to unmask]]
--------------------------------------------------------------------------------
Glycogen Synthase Kinase-3 Is Required for Efficient Dictyostelium
Chemotaxis
Regina Teo, Kimberley J. Lewis, Josephine E. Forde, W. Jonathan Ryves,
Jonathan V. Reddy, Benjamin J. Rogers, and Adrian J. Harwood
Molecular Biology of the Cell (in press) epub 10.1091/mbc.E09-10-0891
Glycogen synthase kinase-3 (GSK3) is a highly conserved protein kinase
that is involved in several important cell signaling pathways and is
associated
with a range of medical conditions. Previous studies indicated a major
role
of the Dictyostelium homologue of GSK3 (gskA) in cell fate determination
during morphogenesis of the fruiting body; however, transcriptomic and
proteomic studies have suggested that GSK3 regulates gene expression
much earlier during Dictyo- stelium development. To investigate a
potential
earlier role of GskA, we examined the effects of loss of gskA on cell
aggregation. We find that cells lacking gskA exhibit poor chemotaxis
toward
cAMP and folate. Mutants fail to activate two important regulatory
signaling
pathways, mediated by phosphatidylinositol 3,4,5-trisphosphate and
target
of rapamycin complex 2, which in combination are required for chemotaxis
and cAMP signaling. These results indicate that GskA is required during
early stages of Dictyostelium development, in which it is necessary for
both chemotaxis and cell signaling.
Submitted by Adrian Harwood [[log in to unmask]]
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[End dictyNews, volume 34, number 19]
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