dictyNews
Electronic Edition
Volume 39, number 25
August 30 2013
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Abstracts
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Inhibitory signalling to the Arp2/3 complex steers cell migration
Irene Dang1, Roman Gorelik1, Carla Sousa-Blin1, Emmanuel Derivery1,
Christophe Guérin2, Joern Linkner3, Maria Nemethova4, Tamara
Tchipysheva5, Valeria Ermilova5, Sophie Vacher6, Julien G. Dumortier7,
Florence A. Giger7, Valérie Campanacci8, Isaline Herrada9, Anne-Gaelle
Planson8, Susan Fetics8, Véronique Henriot1, Violaine David1, Ksenia
Oguievetskaia1, Goran Lakisic1, Fabienne Pierre1, Adeline Boyreau11,
Nadine Peyriéras11, Anika Steffen10, Klemens Rottner10, Sophie
Zinn-Justin9, Jacqueline Cherfils8, Nicolas B. David7, Ivan Bièche6,
Antonina Alexandrova5, J. Victor Small4, Jan Faix3, Laurent Blanchoin2,
Alexis Gautreau1.
1 Group Cytoskeleton in Cell Morphogenesis Laboratoire d’Enzymologie
et Biochimie Structurales, CNRS, Gif-sur-Yvette, France
2 Physics of the Cytoskeleton and Morphogenesis, Grenoble, France
3 Institute for Biophysical Chemistry, Hannover Medical School,
Hannover, Germany
4 Institute of Molecular Biotechnology, Vienna, Austria
5 Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center,
Russian Academy of Medical Sciences, Moscow, Russian Federation
6 INSERM, CNRS, ENS, Institut de Biologie de l'ENS, Paris, France
7 Oncogenetic Laboratory, Institut Curie - Hôpital René Huguenin,
Saint-Cloud, France
8 Laboratoire d’Enzymologie et Biochimie Structurales, CNRS,
Gif-sur-Yvette, France
9 Laboratoire de Biologie Structurale et Radiobiologie, iBiTec-S
and CNRS, CEA Saclay, Gif-sur-Yvette, France
10 Institute of Genetics, University of Bonn, Germany
11 Institut des Systèmes complexes & NeD, Institut de Neurobiologie
Alfred Fessard, CNRS, Gif-sur-Yvette, France.
Nature, in press.
Cell migration requires the generation of branched actin networks
that power the protrusion of the plasma membrane in lamellipodia.
The Arp2/3 complex is the molecular machine that nucleates these
branched actin networks. This machine is activated at the leading
edge of migrating cells by the WAVE complex. The WAVE complex
is itself directly activated by the small GTPase Rac, which induces
lamellipodia. However, how cells regulate the directionality of
migration is poorly understood. Here we identify a novel protein
that inhibits the Arp2/3 complex in vitro, Arpin, and show that Rac
signalling recruits and activates Arpin at the lamellipodial tip, like
WAVE. Consistently, upon depletion of the inhibitory Arpin,
lamellipodia protrude faster and cells migrate faster. The major
role of this inhibitory circuit, however, is to control directional
persistence of migration. Indeed, Arpin depletion in both
mammalian cells and Dictyostelium discoideum amoeba resulted
in straighter trajectories, whereas Arpin microinjection in fish
keratocytes, one of the most persistent systems of cell migration
known, induced these cells to turn. The coexistence of the
Rac-Arpin-Arp2/3 inhibitory circuit with the Rac-WAVE-Arp2/3
activatory circuit can account for this conserved role of Arpin in
steering cell migration. Loss of this inhibitory circuit promotes
exploratory behaviours and might commit carcinoma cells to
the invasive state.
Submitted by Hans Faix [[log in to unmask]]
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A novel human receptor involved in bitter tastant detection
identified using the model organism Dictyostelium discoideum
Steven Robery1, Richard Tyson2, Christopher Dinh3,
Adam Kuspa3, Angelika A. Noegel4, Till Bretschneider2,
Paul L. R. Andrews5, Robin S. B. Williams1*
1. Centre for Biomedical Sciences, School of Biological Sciences,
Royal Holloway University of London, Egham TW20 0EX, UK
2. Molecular Organization and Assembly in Cells, University of
Warwick, Coventry, CV4 7AL, UK
3. Department of Biochemistry and Molecular Biology, Baylor
College of Medicine, Houston, Texas 77030, USA
4. Institute of Biochemistry I, Medical Faculty, University of
Cologne, Cologne, Germany
5. Division of Biomedical Sciences, St George's University of
London, London SW17 0RE, UK
*Corresponding author; [log in to unmask]
Journal of Cell Science, in press
Detection of substances tasting bitter to humans occurs in
diverse organisms including the social amoeba, Dictyostelium
discoideum. To establish a molecular mechanism for bitter
tastant detection in Dictyostelium, we screened a mutant library
for resistance to a commonly used bitter standard, phenylthiourea.
This approach identified a G-protein coupled receptor mutant,
grlJ-, showing a significantly increased tolerance to phenylthiourea
in growth, survival and movement. This mutant was not resistant to
a structurally dissimilar potent bitter tastant, denatonium benzoate,
suggesting it is not a target for at least one other bitter tastant.
Analysis of the cell signalling pathway involved in the detection of
phenylthiourea showed dependence upon heterotrimeric G-protein
and phosphatidylinositol 3-kinase activity, suggesting this signalling
pathway is responsible for phenylthiourea cellular effects. This is
further supported by a phenylthiourea-dependent block in the
transient cAMP-induced production of PIP3 in wild type but not
grlJ- cells. Finally, we have identified an uncharacterized human
protein gamma-aminobutyric acid (GABA) type B receptor subunit 1
isoform with weak homology to GrlJ that restored grlJ- sensitivity to
phenylthiourea in cell movement and PIP3 regulation. Our data thus
identifies a novel pathway for the detection of the standard bitter
tastant, phenylthiourea, in Dictyostelium and implicates a poorly
characterized human protein in phenylthiourea dependent cell
responses.
Submitted by Robin Williams [[log in to unmask]]
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[End dictyNews, volume 39, number 25]
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