dictyNews
Electronic Edition
Volume 34, number 9
March 12, 2010
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Abstracts
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A myosin IK-Abp1-PakB circuit acts as a switch to regulate phagocytosis
efficiency
Régis Dieckmann, Yosuke von Heyden, Claudia Kistler, Navin Gopaldass,
Stéphanie Hausherr, Scott William Crawley, Eva C. Schwarz, Ralph P.
Diensthuber, Graham P. Côté, Georgios Tsiavaliaris, and Thierry Soldati
Molecular Biology of the Cell, in press
Actin dynamics and myosin contractile forces are necessary for formation
and closure of the phagocytic cup. In Dictyostelium, the actin-binding
protein
Abp1 and myosinIK are enriched in the closing cup and especially at an
actin-dense constriction furrow formed around the neck of engulfed
budded
yeasts. This phagocytic furrow consists of concentric overlapping
rings of
MyoK, Abp1, Arp3, coronin and myosin II, following an order strikingly
reminiscent of the overall organization of the lamellipodium of
migrating
cells. Mutation analyses of MyoK revealed that both a C-terminal
farnesylation membrane anchor and a Gly-Pro-Arg domain that interacts
with profilin and Abp1, were necessary for proper localization in the
furrow
and efficient phagocytosis. Consequently, we measured the binding
affinities
of these interactions and unraveled further interactions with profilins,
dynamin A and PakB. Due to the redundancy of the interaction network, we
hypothesize that MyoK and Abp1 are restricted to regulatory roles and
might
affect the dynamic of cup progression. Indeed, phagocytic uptake was
regulated antagonistically by MyoK and Abp1. MyoK is phosphorylated by
PakB and positively regulates phagocytosis, whereas binding of Abp1
negatively regulates PakB and MyoK. We conclude that a MyoK-Abp1-PakB
circuit acts as a switch regulating phagocytosis efficiency of large
particles.
Submitted by Thierry Soldati [[log in to unmask]]
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Bimodal analysis reveals a general scaling law governing non-directed
and chemotactic cell motility
J. Scott Gruver1*, Alka A. Potdar2,4*, Junhwan Jeon2,4, Jiqing Sai3,
Bridget Anderson5, Donna Webb3,5,6, Ann Richmond3,7, Vito Quaranta3,
Peter T. Cummings2,4,8, and Chang Chung1,5, #
1Department of Pharmacology,
2Vanderbilt Integrative Cancer Biology Center,
3Department of Cancer Biology, Vanderbilt University Medical Center,
Nashville, TN 37232,
4Department of Chemical and Biomolecular Engineering,
5Department of Biological Sciences, Vanderbilt University,
Nashville, TN, 37235,
6Vanderbilt Kennedy Center for Research on Human Development,
Nashville TN, 37235,
7Department of Veterans Affairs (Nashville, TN),
8Center for Nanophase Materials Sciences, Oak Ridge National Laboratory,
Oak Ridge, TN 37831
Biophy. J., in press
Cell motility is a fundamental process with relevance to embryonic
development,
immune response, and metastasis. Cells move either spontaneously, in a
non-directed fashion, or in response to chemotactic signals, in a
directed fashion.
Even though they are often studied separately, both forms of motility
share many
complex processes at the molecular and subcellular scale, e.g.,
orchestrated
cytoskeletal rearrangements and polarization. In addition, at the
cellular level
both types of motility include persistent runs interspersed with
reorientation
pauses(1-4). Because there is a great range of variability in motility
among
different cell types, a key challenge in the field is to integrate
these multi-scale
processes into a coherent framework. We analyzed the motility of
Dictyostelium
cells with bimodal analysis, a method that compares time spent in
persistent
versus reorientation mode. Unexpectedly, we found that reorientation
time is
coupled with persistent time in an inverse correlation and,
surprisingly, the
inverse correlation holds for both non-directed and chemotactic
motility, so that
the full range of Dictyostelium motility can be described by a single
scaling
relationship. Additionally, we found an identical scaling relationship
for three
human cell lines, indicating that the coupling of reorientation and
persistence
holds across species and making it possible to describe the complexity
of cell
motility in a surprisingly general and simple manner. With this new
perspective,
we analyzed the motility of Dictyostelium mutants, and found four in
which the
coupling between two modes was altered. Our results point to a
fundamental
underlying principle, described by a simple scaling law, unifying
mechanisms
of eukaryotic cell motility at several scales.
Submitted by Chang Chung [[log in to unmask]]
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New components of the Dictyostelium PKA pathway revealed by Bayesian
analysis of expression data
Anup Parikh, Eryong Huang, Christopher Dinh, Blaz Zupan, Adam Kuspa,
Devika Subramanian and Gad Shaulsky
Baylor College of Medicine, University of Ljubljana and Rice University
BMC Bioinformatics, in press
Background
Identifying candidate genes in genetic networks is important for
understanding
regulation and biological function. Large gene expression datasets
contain
relevant information about genetic networks, but mining the data is
not a trivial
task. Algorithms that infer Bayesian networks from expression data are
powerful
tools for learning complex genetic networks, since they can
incorporate prior
knowledge and uncover higher-order dependencies among genes. However,
these algorithms are computationally demanding, so novel techniques
that allow
targeted exploration for discovering new members of known pathways are
essential.
Results
Here we describe a Bayesian network approach that addresses a specific
network
within a large dataset to discover new components. Our algorithm draws
individual
genes from a large gene-expression repository, and ranks them as
potential
members of a known pathway. We apply this method to discover new
components
of the cAMP-dependent protein kinase (PKA) pathway, a central
regulator of
Dictyostelium discoideum development. The PKA network is well studied in
D. discoideum but the transcriptional networks that regulate PKA
activity and the
transcriptional outcomes of PKA function are largely unknown. Most of
the genes
highly ranked by our method encode either known components of the PKA
pathway or are good candidates. We tested 5 uncharacterized highly
ranked
genes by creating mutant strains and identified a candidate cAMP-
response
element-binding protein, yet undiscovered in D. discoideum, and a
histidine
kinase, a candidate upstream regulator of PKA activity.
Conclusions
The single-gene expansion method is useful in identifying new
components of
known pathways. The method takes advantage of the Bayesian framework to
incorporate prior biological knowledge and discovers higher-order
dependencies
among genes while greatly reducing the computational resources
required to
process high-throughput datasets.
Submitted by Gad Shaulsky [[log in to unmask]]
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Conserved Developmental Transcriptomes in Evolutionary Divergent
Species
Anup Parikh*, Edward Roshan Mirada*, Mariko Katoh-Kurasawa,
Danny Fuller, Gregor Rot, Lan Zagar, Tomaz Curk, Richard Sucgang,
Rui Chen, Blaz Zupan, William F. Loomis, Adam Kuspa and Gad Shaulsky
* equal contribution
Baylor College of Medicine, UC San Diego, and University of Ljubljana
Genome Biology, in press
Background
Evolutionary divergent organisms often share developmental anatomies
despite vast differences between their genome sequences. The social
amoebae Dictyostelium discoideum and Dictyostelium purpureum have
similar developmental morphologies although their genomes are as
divergent as those of man and jawed fish.
Results
Here we show that the anatomical similarities are accompanied by
extensive
transcriptome conservation. Using RNA sequencing we compared the
abundance and developmental regulation of all the transcripts in the two
species. In both species, most genes are developmentally regulated and
the
greatest expression changes occur during the transition from
unicellularity
to multicellularity. The developmental regulation of transcription is
highly
conserved between orthologs in the two species. In addition to timing of
expression, the level of mRNA production is also conserved between
orthologs and is consistent with the intuitive notion that transcript
abundance
correlates with the amount of protein required. Furthermore, the
conservation of transcriptomes extends to cell-type specific expression.
Conclusions
These findings suggest that developmental programs are remarkably
conserved at the transcriptome level, considering the great evolutionary
distance between the genomes. Moreover, this transcriptional
conservation
may be responsible for the similar developmental anatomies of
Dictyostelium discoideum and Dictyostelium purpureum.
Submitted by Gad Shaulsky [[log in to unmask]]
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[End dictyNews, volume 34, number 9]
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