Dicty News
Electronic Edition
Volume 23, number 11
October 01, 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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Localized Ras signaling at the leading edge regulates PI3K, cell polarity,
and directional cell movement


Atsuo T. Sasaki, Cheryl Chun, Kosuke Takeda, and Richard A. Firtel
Section of Cell and Developmental Biology, Division of Biological Sciences
and Center for Molecular Genetics, University of California,
San Diego, 9500 Gilman Drive, La Jolla,
California 92093-0380

J. Cell Biology, in press


During chemotaxis, receptors and heterotrimeric G-protein subunits are
distributed and activated almost uniformly along the cell membrane, whereas
PI(3,4,5)P3, the product of PI3K, accumulates locally at the leading edge.
The key intermediate event that creates this strong PI(3,4,5)P3 asymmetry
remains unclear. We show that Ras is rapidly and transiently activated in
response to chemoattractant stimulation and regulates PI3K activity. Ras
activation occurs at the leading edge of chemotaxing cells, and this local
activation is independent of the F-actin cytoskeleton, whereas PI3K
localization is dependent on F-actin polymerization. Inhibition of Ras
results in severe defects in directional movement, indicating that Ras is
an upstream component of the cellās compass. These results support a
mechanism by which localized Ras activation mediates leading edge formation
through activation of basal PI3K present on the plasma membrane and other
Ras effectors required for chemotaxis. A feedback loop, mediated through
localized F-actin polymerization, recruits cytosolic PI3K to the leading
edge to amplify the signal. 
 
 
Submitted by:  [Rick Firtel <rafirtel@ucsd.edu]

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Cell shape regulation and co-translocation of actin and adenosyl
homocysteinase in response to intermediate hypertonicity.

Yohko Yamada 1 and Masazumi Sameshima 2
1 Department of Biology, Graduate School of Science, Osaka University.
2 Department of Biofunctional Science, Faculty of Agriculture and Life
Science, Hirosaki University.

FEMS Microbiology Letters, Volume 238, 2004, Pages 417-422 


Hypertonic stimulation induced association of S-adenosyl-L-homocysteine
hydrolase (SAHH) with the F-actin-rich cell cortex in Dictyostelium. At
intermediate, but not higher, levels of hypertonicity, SAHH further
translocated from the cortex to the cytosol in company with a fraction of
actin and cofilin. At the same time the cells rounded up. Acidification of
the cells stimulated both the cell rounding and the translocation of actin
and SAHH, whereas alkalinization retarded these responses, suggesting that
cellular pH is involved in their control. On the other hand, mutant analysis
suggested that neither cGMP signaling nor conventional myosin is required.


Submitted by:  Masazumi Sameshima [msameshi@cc.hirosaki-u.ac.jp]

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Two complementary, local excitation, global inhibition mechanisms acting in
parallel can explain the chemoattractant-induced regulation of PI(3,4,5)P3
response in Dictyostelium cells

Lan Ma1, Chris Janetopoulos2, Liu Yang1, Peter N. Devreotes2 and Pablo A.
Iglesias1,3


1 Department of Electrical and Computer Engineering, Johns Hopkins University,
3400 N. Charles St., Baltimore, MD 21218

2 Department of Cell Biology, Johns Hopkins University School of Medicine,
725 N. Wolfe St., Baltimore, MD 21205

Biophysical Journal, in press


Chemotaxing cells, such as Dictyostelium and mammalian neutrophils, sense
shallow chemoattractant gradients and respond with highly polarized changes
in cell morphology and motility. Uniform chemoattractant stimulation induces
the transient translocations of several downstream signaling components,
including PI3K, PTEN, and PI(3,4,5)P3.  In contrast, static spatial
chemoattractant gradients elicit the persistent, amplified localization of
these molecules.  We have proposed a model in which the response to
chemoattractant is regulated by a balance of a local excitation and a
global inhibition, both which are controlled by receptor occupancy.  This
model can account for both the transient and spatial responses to
chemoattractants, but alone does not amplify the external gradient. In this
paper we develop a model in which parallel local excitation, global
inhibition mechanisms control the membrane binding of PI3K and PTEN.
Together, the action of these enzymes induces an amplified PI(3,4,5)P3
response that agrees  quantitatively with experimentally obtained PH-GFP
distributions in latrunculin-treated cells. We compare the model's 
performance with that of several mutants in which one or both of the enzymes
are disrupted. The model accounts for the observed response to multiple,
simultaneous chemoattractant cues and can recreate the cellular response to
combinations of temporal and spatial stimuli. Finally, we use the model to
predict the response of a cell where only a fraction is stimulated by a
saturating dose of chemoattractant.


Submitted by:  Pablo A. Iglesias" [pi@jhu.edu]

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[End Dicty News, volume 23, number 11]