dictyNews Electronic Edition Volume 35, number 12 October 29, 2010 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. Follow dictyBase on twitter: http://twitter.com/dictybase ========= Abstracts ========= The Ras related GTPase Miro is not required for mitochondrial transport in Dictyostelium discoideum Georgia Vlahou, Marek Elias, Jürgen-Christoph von Kleist-Retzow, Rudolf J. Wiesner and Francisco Rivero European Journal of Cell Biology, in press Ras-related GTPases of the Miro family have been implicated in mitochondrial homeostasis and microtubule-dependent transport. They consist of two GTP-binding domains separated by calcium-binding motifs and of a C-terminal transmembrane domain that targets the protein to the outer mitochondrial membrane. We disrupted the single Miro-encoding gene in Dictyostelium discoideum and observed a substantial growth defect that we attribute to a decreased mitochondrial mass and cellular ATP content. However, mutant cells even showed an increased rate of oxygen consumption, while glucose consumption, mitochondrial transmembrane potential and production of reactive oxygen species were unaltered. Processes characteristic of the multicellular stage of D. discoideum life cycle were also unaltered. Although mitochondria occasionally use microtubules for transport in D. discoideum, their size and distribution were not visibly affected. We found Miro in all branches of the eukaryotic tree with the exception of a few protist lineages (mainly those lacking typical mitochondria). Trypanosomatids and ciliates possess structurally unique homologs lacking the N-terminal or the C-terminal GTPase domain, respectively. We propose that in D. discoideum, as in yeasts and plants, Miro plays roles in mitochondrial homeostasis, but the ability to build a complex that regulates its association to kinesin for microtubule-dependent transport probably arose in metazoans. Submitted by Francisco Rivero [f.rivero-crespo@hull.ac.uk] -------------------------------------------------------------------------------- Lead genetic studies in Dictyostelium discoideum and translational studies in human cells demonstrate that sphingolipids are key regulators of sensitivity to cisplatin and other anticancer drugs Stephen Alexander and Hannah Alexander Division of Biological Sciences, University of Missouri, Columbia, MO 65211 USA Seminars in Cell and Developmental Biology, in press. A Dictyostelium discoideum mutant with a disruption in the sphingosine-1-phosphate (S-1-P) lyase gene was obtained in an unbiased genetic analysis, using random insertional mutagenesis, for mutants with increased resistance to the widely used cancer chemotherapeutic drug cisplatin. This finding opened the way to extensive studies in both D. discoideum and human cells on the role and mechanism of action of the bioactive sphingolipids S-1-P and ceramide in regulating the response to chemotherapeutic drugs. These studies showed that the levels of activities of the sphingolipid metabolizing enzymes S-1-P lyase, sphingosine kinase and ceramide synthase, affect whether a cell dies or lives in the presence of specific drugs. The demonstration that multiple enzymes of this biochemical pathway were involved in regulating drug sensitivity provided new opportunities to test whether pharmacological intervention might increase sensitivity. Thus it is of considerable clinical significance that pharmacological inhibition of sphingosine kinase synergistically sensitizes cells to cisplatin, both in D. discoideum and human cells. Linkage to the p38 MAP kinase and protein kinase C (PKC) signaling pathways has been demonstrated. This work demonstrates the utility of D. discoideum as a lead genetic system to interrogate molecular mechanisms controlling the sensitivity of tumor cells to chemotherapeutic agents and for determining novel ways of increasing efficacy. The D. discoideum system could be easily adapted to a high throughput screen for novel chemotherapeutic agents. Submitted by Steve Alexander [AlexanderSt@missouri.edu] ============================================================== [End dictyNews, volume 35, number 12]