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dictyNews Volume 41 Number 16
dictyNews
Electronic Edition
Volume 41, number 16
July 31, 2015
Please submit abstracts of your papers as soon as they have been
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Abstracts
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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]
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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]
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[End dictyNews, volume 41, number 16]
