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dictyNews Volume 30 Number 16
dictyNews
Electronic Edition
Volume 30, number 16
May 16, 2008
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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Kim J, Bates DG, Postlethwaite I, Heslop-Harrison P, Cho K-H
Linear time-varying models can reveal nonlinear interactions of
biomolecular regulatory networks using multiple time-series data
Bioinformatics, in press
Motivation: Inherent nonlinearities in biomolecular interactions make
the identification of network interactions difficult. One of the
principal problems is that all methods based on the use of linear
time invariant models will have fundamental limitations in their
capability to infer certain nonlinear network interactions. Another
difficulty is the multiplicity of possible solutions, since, for a
given data set, there may be many different possible networks which
generate the same time-series expression profiles.
Results: A novel algorithm for the inference of biomolecular interaction
networks from temporal expression data is presented. Linear time-varying
models, which can represent a much wider class of time-series data than
linear time-invariant models, are employed in the algorithm. From
time-series expression profiles, the model parameters are identified
by solving a nonlinear optimisation problem. In order to systematically
reduce the set of possible solutions for the optimisation problem, a
filtering process is performed using a phase-portrait analysis with
random numerical perturbations. The proposed approach has the advantages
of not requiring the system to be in a stable steady-state, of using
time-series profiles which have been generated by a single experiment,
and of allowing nonlinear network interactions to be identified. The
ability of the proposed algorithm to correctly infer network interactions
is illustrated by its application to three examples: a nonlinear model
for cAMP oscillations in Dictyostelium discoideum, the cell-cycle data
for Saccharomyces cerevisiae and a large-scale nonlinear model of a
group of synchronised Dictyostelium cells.
Submitted by: Pat Heslop-Harrisonr [phh4@le.ac.uk]
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Dephosphorylation of 2,3-bisphosphoglycerate by MIPP expands the regulatory
capacity of the Rapoport–Luebering glycolytic shunt
Jaiesoon Cho*†, Jason S. King‡§, Xun Qian*, Adrian J. Harwood‡, and
Stephen B. Shears
PNAS vol. 105 (16) pp5998–6003
The Rapoport–Luebering glycolytic bypass comprises evolutionarily conserved
reactions that generate and dephosphorylate 2,3-bisphosphoglycerate (2,3-BPG).
For>30 years, these reactions have been considered the responsibility of a
single enzyme, the 2,3-BPG synthase/2-phosphatase (BPGM). Here, we show that
Dictyostelium, birds, and mammals contain an additional 2,3-BPG phosphatase
that, unlike BPGM, removes the 3-phosphate. This discovery reveals that the
glycolytic pathway can bypass the formation of 3-phosphoglycerate, which
is a precursor for serine biosynthesis and an activator of AMP-activated
protein kinase. Our 2,3-BPG phosphatase activity is encoded by the previously
identified gene for multiple inositol polyphosphate phosphatase (MIPP1),
which we now show to have dual substrate specificity. By genetically
manipulating Mipp1 expression in Dictyostelium, we demonstrated that this
enzyme provides physiologically relevant regulation of cellular 2,3-BPG
content. Mammalian erythrocytes possess the highest content of 2,3-BPG,
which controls oxygen binding to hemoglobin. We determined that total MIPP1
activity in erythrocytes at 37°C is 0.6 mmol 2,3-BPG hydrolyzed per liter
of cells per h, matching previously published estimates of the phosphatase
activity of BPGM. MIPP1 is active at 4°C, revealing a clinically significant
contribution to 2,3-BPG loss during the storage of erythrocytes for
transfusion. Hydrolysis of 2,3-BPG by human MIPP1 is sensitive to
physiologic alkalosis; activity decreases 50% when pH rises from 7.0 to 7.4.
This phenomenon provides a homeostatic mechanism for elevating 2,3-BPG
levels, thereby enhancing oxygen release to tissues. Our data indicate
greater biological significance of the Rapoport–Luebering shunt than
previously considered.
Submitted by: Adrian Harwood [harwoodaj@cf.ac.uk]
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MPL1, the novel phosphatase with Leucine-Rich-Repeats, is essential for proper
ERK2 phosphorylation and cell motility.
Marbelys Rodriguez, Bohye Kim, Nam-Sihk Lee, Sudhakar Veeranki, and Leung Kim*
Dept of Biological Sciences, Florida International University, Miami, FL 33199
* To whom correspondence should be addressed. Email: kiml@fiu.edu.
Eukaryotic Cell, in press
The novel Dictyostelium phosphatase Mpl1 contains six Leucine-Rich-Repeats
at the amino-terminal end and a phosphatase domain at the carboxyl end.
Similarly architectured phosphatases exist among other protozoa such as
Entamoeba histolytica, Leishmania major, and Trypanosoma cruzi. Mpl1 was
strongly induced after 5 hours of development; ablation by homologous
recombination led to defective streaming and aggregation during development.
In addition, cAMP pulsed mpl1- cells showed reduced random and directional
motility. At the molecular level, mpl1- cells displayed higher prestimulus and
persistent post-stimulus ERK2 phosphorylation in response to cAMP stimulation.
Consistent with their phenotype of persistent ERK2 phosphorylation, mpl1- cells
also displayed an aberrant pattern of cAMP production, resembling that of the
regA- cells. Reintroduction of a full length Mpl1 into mpl1- cells restored
aggregation, ERK2 regulation, random and directional motility, and cAMP
production similar to wild type cells. We propose that MPL1 is a novel
phosphatase essential for proper regulation of ERK2 phosphorylation and
optimal motility during development.
Submitted by: Marbelys Rodriguez [mrodr126@fiu.edu]
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[End dictyNews, volume 30, number 16]
