dictyNews Volume 27 Number 09

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dictyNews 
Electronic Edition 
Volume 27, number 9 
September 15, 2006 

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. 

 
============= 
  Abstracts 
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Role of RacC for the regulation of WASP and PI3 kinase during chemotaxis  
of Dictyostelium 

Ji W. Han1, Laura Leeper1, Francisco Rivero2, Chang Y. Chung1* 
1Department of Pharmacology, Vanderbilt University Medical Center,  
Nashville TN 37232-6600  
2Zentrum fŸr Biochemie and Zentrum fŸr Molekulare Medizin, Medizinische  
FakultŠt, UniversitŠt zu Kšln, Joseph-Stlzmann-Str. 52, 50931 Kšln, Germany 

 
Journal of Biological Chemistry, in press 

WASP family proteins are key players for connecting multiple signaling  
pathways to F-actin polymerization. To dissect the highly integrated  
signaling pathways controlling WASP activity, we identified a Rac protein  
that binds to the GTPase-binding domain of WASP.  Using two-hybrid and  
FRET-based functional assays, we identified RacC as a major regulator of  
WASP.  RacC stimulates F-actin assembly in cell-free systems in a  
WASP-dependent manner. A FRET-based microscopy approach showed local  
activation of RacC at the leading edge of chemotaxing cells.  Cells  
overexpressing RacC exhibit a significant increase in the level of F-actin  
polymerization upon cAMP stimulation, which can be blocked by a PI3 kinase  
inhibitor.  Membrane translocation of PI3-kinase and PI(3,4,5)P3 reporter  
is absent in racC null cells.  Cells overexpressing dominant negative RacC  
mutants and racC null cells move at a significantly slower speed and show  
a poor directionality during chemotaxis.  Our results suggest that RacC  
plays an important role in PI3 kinase activation and WASP activation for  
dynamic regulation of F-actin assembly during Dictyostelium chemotaxis. 

 
Submitted by: Chang Chung [chang.chung@vanderbilt.edu] 
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Nonadaptive Regulation of ERK2 in Dictyostelium: Implications for Mechanisms  
of cAMP Relay.  

Brzostowski JA and Kimmel AR. 

Laboratory of Cellular and Developmental Biology, National Institute of  
Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 
Bethesda, MD 20892-8028; Laboratory of Immunogenetics, National Institute  
of Allergy and Infectious Diseases, National Institutes of Health,  
Rockville, MD 20852. 

 
Mol Biol Cell. 2006 Jul 26; (Epub ahead of print) 

It is assumed that ERK2 in Dictyostelium is subject to adaptive regulation  
in response to constant extracellular ligand stimulation. We now show, to  
the contrary, that ERK2 remains active under continuous stimulation,  
differing from most ligand-activated pathways in chemotactically-competent  
Dictyostelium and other cells. We show that the upstream phosphorylation  
pathway, responsible for ERK2 activation, transiently responds to receptor  
stimulation, whereas ERK2 de-phosphorylation (deactivation) is inhibited  
by continuous stimulation. We argue that the net result of these two  
regulatory actions is a persistently active ERK2 pathway when the  
extracellular ligand (i.e. cAMP) concentration is held constant, and that  
oscillatory production/destruction of secreted cAMP in chemotaxing cells  
accounts for the observed oscillatory activity of ERK2. We also show that  
pathways controlling seven-transmembrane receptor (7-TMR) ERK2  
activation/deactivation function independently of G proteins and  
ligand-induced production of intracellular cAMP and the consequent  
activation of PKA. Finally, we propose that this regulation enables ERK2  
to function both in an oscillatory manner, critical for chemotaxis, and  
in a persistent manner, necessary for gene expression, as secreted ligand  
concentration increases during later development. This work redefines  
mechanisms of ERK2 regulation by 7-TMR signaling in Dictyostelium and  
establishes new implications for control of signal-relay during chemotaxis. 

 
Submitted by: Joe Brzostowski [jb363a@nih.gov] 
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[End dictyNews, volume 27, number 9]