dictyNews Volume 39 Number 25

eZine lover (@eZine)

Published in 

Dicty News

 · 10 months ago

dictyNews 
Electronic Edition 
Volume 39, number 25 
August 30 2013 

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 
========= 

 

Inhibitory signalling to the Arp2/3 complex steers cell migration 

 
Irene Dang1, Roman Gorelik1, Carla Sousa-Blin1, Emmanuel Derivery1,  
Christophe GuŽrin2, Joern Linkner3, Maria Nemethova4, Tamara  
Tchipysheva5, Valeria Ermilova5, Sophie Vacher6, Julien G. Dumortier7,  
Florence A. Giger7, ValŽrie Campanacci8, Isaline Herrada9, Anne-Gaelle  
Planson8, Susan Fetics8, VŽronique Henriot1, Violaine David1, Ksenia  
Oguievetskaia1, Goran Lakisic1, Fabienne Pierre1, Adeline Boyreau11,  
Nadine PeyriŽras11, Anika Steffen10, Klemens Rottner10, Sophie  
Zinn-Justin9, Jacqueline Cherfils8, Nicolas B. David7, Ivan Biche6,  
Antonina Alexandrova5, J. Victor Small4, Jan Faix3, Laurent Blanchoin2,  
Alexis Gautreau1. 

1 Group Cytoskeleton in Cell Morphogenesis Laboratoire dÕEnzymologie  
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 - H™pital RenŽ Huguenin,  
Saint-Cloud, France  
8 Laboratoire dÕEnzymologie 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 Systmes 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 [faix.jan@mh-hannover.de] 
--------------------------------------------------------------------------- 

 
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; robin.williams@rhul.ac.uk 

 
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 [robin.williams@rhul.ac.uk] 
============================================================== 
[End dictyNews, volume 39, number 25]