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. ========= Abstracts ========= 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] -------------------------------------------------------------------------------- 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] -------------------------------------------------------------------------------- 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] ============================================================== [End dictyNews, volume 29, number 6]