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dictyNews Volume 29 Number 06
dictyNews
Electronic Edition
Volume 29, number 6
August 24, 2007
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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Global Transcriptional Responses to Cisplatin in Dictyostelium discoideum
Identify Potential Drug Targets
Nancy Van Driessche, Hannah Alexander, Junxia Min, Adam Kuspa,
Stephen Alexander* and Gad Shaulsky*
* corresponding authors
Department of Molecular and Human Genetics, One Baylor Plaza, Baylor
College of Medicine, Houston, TX 77030
Division of Biological Sciences, University of Missouri, Columbia,
MO 65211-7400
Department of Biochemistry and Molecular Biology, One Baylor Plaza,
Baylor College of Medicine, Houston, TX 77030
PNAS, in press
Dictyostelium discoideum is a useful model for studying mechanisms of
cisplatin drug sensitivity. Our previous findings, that mutations in
sphingolipid-metabolism genes confer cisplatin resistance in D. discoideum
and in human cells, raised interest in the resistance mechanisms and their
implications for cisplatin chemotherapy. Here we used expression microarrays
to monitor physiological changes and to identify pathways that are affected
by cisplatin treatment of D. discoideum. We found over 400 genes whose
regulation was altered by cisplatin treatment of wild type cells, including
groups of genes that participate in cell proliferation and in nucleotide and
protein metabolism, showing that the cisplatin response is orderly and
multifaceted. Transcriptional profiling of two isogenic cisplatin-resistant
mutants, impaired in different sphingolipid metabolism steps, showed that
the effect of cisplatin treatment was greater than the effect of the
mutations, indicating that cisplatin-resistance in the mutants is due to
specific abilities to overcome the drug effects rather than to general drug
insensitivity. Nevertheless, the mutants exhibited significantly different
responses to cisplatin compared to the parent and over 200 genes accounted
for that difference. Mutations in 5 cisplatin-response genes (sgkB, csbA,
acbA, smlA and atg8) resulted in altered drug sensitivity, implicating novel
pathways in cisplatin response. Our data illustrate how modeling complex
cellular responses to drugs in genetically stable and tractable systems can
uncover new targets with the potential for improving chemotherapy.
Submitted by: Gad Shaulsky [gadi@bcm.tmc.edu]
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Calmodulin-binding proteins in the model organism Dictyostelium:
A complete & critical review
Andrew Catalano and Danton H. O'Day1
Department of Biology, University of Toronto at Mississauga, 3359
Mississauga Rd. Mississauga, ON. Canada L5L 1C6
1Contact information: doday@utm.utoronto.ca
Cellular Signalling , in press
1. Introduction
2. Dictyostelium CaM
3. The discovery of CaMBPs: a short history
4. CaM-dependent phosphorylation/dephosphorylation
5. The CaMBPs of Dictyostelium
5.1. Calcineurin
5.2. Ribosomal subunit protein L19
5.3. DGAP1
5.4. Nucleomorphin
5.5. Nucleomorphin and multinuclearity
5.6. Histone H1 (DdH1)
5.7. Phosphoglycerate kinase (DdPGK)
5.8. Thymidine kinase 1 (DdTK1)
5.9. VwkA: a novel alpha-kinase
5.10. cmbB: an IP-22 motif protein
5.11. Spectrin (fodrin)
5.12. DWWA: a CaMBP involved in scission
5.13. Myosins: Ca2+-independent CaMBPs
5.14. Functions of myosin I and II
5.15. Myosin light chains
5.16. Myosin I regulation via kinases
5.17. Myosin II regulation via kinases
5.18. Light chain regulation
5.19. CaM and myosin function: a model
6. Conclusion
Calmodulin is an essential protein in the model organism Dictyostelium
discoideum. As in other organisms, this small, calcium-regulated protein
mediates a diversity of cellular events including chemotaxis, spore
germination, and fertilization. Calmodulin works in a calcium-dependent
or -independent manner by binding to and regulating the activity of target
proteins called calmodulin-binding proteins. Profiling suggests that
Dictyostelium has 60 or more calmodulin-binding proteins with specific
subcellular localizations. In spite of the central importance of
calmodulin, the study of these target proteins is still in its infancy.
Here we critically review the history and state of the art of research
into all of the identified and presumptive calmodulin-binding proteins
of Dictyostelium detailing what is known about each one with suggestions
for future research. Two individual calmodulin-binding proteins, the
classic enzyme calcineurin A (CNA; protein phosphatase 2B) and the
nuclear protein nucleomorphin (NumA), which is a regulator of nuclear
number, have been particularly well studied. Research on the role of
calmodulin in the function and regulation of the various myosins of
Dictyostelium, especially during motility and chemotaxis, suggests this
is an area in which future active study would be particularly valuable.
A general, hypothetical model for the role of calmodulin in myosin
regulation is proposed.
Submitted by: Danton H. O'Day [doday@utm.utoronto.ca]
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High-throughput analysis of spatio-temporal dynamics in Dictyostelium
Satoshi Sawai, Xiao-Juan Guan, Adam Kuspa and Edward C Cox
Genome Biology 2007, 8:R144 (available online)
http://genomebiology.com/2007/8/7/R144
We demonstrate a time-lapse video approach that allows rapid examination
of the spatio-temporal dynamics of Dictyostelium cell populations.
Quantitative information was gathered by sampling life histories of more
than 2,000 mutant clones from a large mutagenesis collection. Approximately
4% of the clonal lines showed a mutant phenotype at one stage. Many of
these could be ordered by clustering into functional groups. The dataset
allows one to search and retrieve movies on a gene-by-gene and
phenotype-by-phenotype basis.
Submitted by: Satoshi Sawai [ssawai@complex.c.u-tokyo.ac.jp]
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[End dictyNews, volume 29, number 6]
