dictyNews Electronic Edition Volume 41, number 16 July 31, 2015 Please submit abstracts of your papers as soon as they have been accepted for publication 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 ========= Dictyostelium Nramp1, structurally and functionally close to mammalian DMT1 transporter, mediates phagosomal iron efflux. Simona Buracco1, Barbara Peracino1, Raffaella Cinquetti#, Elena Signoretto*, Alessandra Vollero#, Francesca Imperiali#, Michela Castagna*, Elena Bossi# and Salvatore Bozzaro1 1 Department of Clinical and Biological Sciences, University of Torino, AOU S. Luigi, 10043 Orbassano, Italy, #Department of Biotechnology and Life Sciences, University of Insubria, Via J. H. Dunant 3, 21100 Varese (Italy) and *Department of Pharmacological and Biomolecular Sciences, Universita degli Studi di Milano, Via Trentacoste 2, 20133 Milano (Italy) J. Cell Sci., in press The Nramp (Slc11) protein family is widespread in bacteria and eucaryotes, and mediates transport of divalent metals across cellular membranes. The social amoeba Dictyostelium discoideum harbours two Nramp proteins. Nramp1, like its mammalian ortholog, is recruited to phagosomal and macropinosomal membranes, and confers resistance to pathogenic bacteria. Nramp2 is located exclusively in the contractile vacuole membrane and controls, synergistically with Nramp1, iron homeostasis. It has long been debated whether mammalian Nramp1 mediates iron import or export from phagosomes. By selectively loading the iron-chelating fluorochrome calcein in macropinosomes, we show that Dictyostelium Nramp1 mediates iron efflux from macropinosomes in vivo. To gain insight in ion selectivity and transport mechanism, the proteins were expressed in Xenopus oocytes. Using a novel assay with calcein, electrophysiological and radiochemical assays, we show that Nramp1, similarly to rat DMT1, transports iron(II) and manganese, not iron(III) or copper. Metal ion transport is electrogenic and proton-dependent. By contrast, Nramp2 transports only iron(II) in a non-electrogenic and proton-independent way. These differences reflect evolutionary divergence of the prototypical Nramp2 protein sequence compared to the archetypical Nramp1 and DMT1 proteins. Submitted by Salvo Bozzaro [salvatore.bozzaro@unito.it] ---------------------------------------------------------------------- Matthew C. Walker and Robin S.B. Williams New experimental therapies for status epilepticus in preclinical development Epilepsy Behav, in press This article is part of a Special Issue entitled "Status Epilepticus" Starting with the established antiepileptic drug, valproic acid, we have taken a novel approach to develop new antiseizure drugs that may be effective in status epilepticus. We first identified that valproic acid has a potent effect on a biochemical pathway, the phosphoinositide pathway, in Dictyostelium discoideum, and we demonstrated that this may relate to its mechanism of action against seizures in mammalian systems. Through screening in this pathway, we have identified a large array of fatty acids and fatty acid derivatives with antiseizure potential. These were then evaluated in an in vitro mammalian system. One compound that we identified through this process is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids that are mediating the antiseizure effect of this diet. We further tested two of the more potent compounds in an in vivo model of status epilepticus and demonstrated that they were more effective than valproic acid in treating the status epilepticus. Submitted by Robin williams[Robin.Williams@rhul.ac.uk] ============================================================== [End dictyNews, volume 41, number 16]