dictyNews
Electronic Edition
Volume 40, number 2
January 10, 2014

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Abstracts
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PIP3-dependent macropinocytosis is incompatible with chemotaxis 

Douwe M. Veltman(1), Michael G. Lemieux (2), David A. Knecht (2) 
and Robert H. Insall (1)* 

(1) Beatson Institute for Cancer Research, Switchback Road, 
Glasgow G61 1BD, UK 
(2) Department of Molecular and Cell Biology, University of Connecticut, 
Storrs, CT 06269, U.S.A.


Journal of Cell Biology, in press

In eukaryotic chemotaxis, the mechanisms connecting external signals to 
the motile apparatus remain unclear. The role of the lipid PIP3 has been 
particularly controversial. PIP3 has many cellular roles, notably in growth 
control and macropinocytosis as well as cell motility. Here we show that 
PIP3 is not only unnecessary for Dictyostelium to migrate towards folate, 
but actively inhibits chemotaxis. We find that macropinosomes, but not 
pseudopods, in growing cells are dependent on PIP3. PIP3 patches in 
these cells show no directional bias, and overall only PIP3-free pseudopods 
orient up-gradient. The pseudopod driver SCAR/WAVE is not recruited to 
centre of PIP3 patches, just the edges, where it causes macropinosome 
formation. Wild type cells, unlike the widely-used axenic mutants, show little 
macropinocytosis and few large PIP3 patches, but migrate more efficiently 
towards folate. Tellingly, folate chemotaxis in axenic cells is rescued by 
knocking out PI3-kinases. Thus PIP3 promotes macropinocytosis and 
interferes with pseudopod orientation during chemotaxis of growing cells. 


Submitted by Douwe Veltman [[log in to unmask]]
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Cell-to-cell coordination for the spontaneous cAMP oscillation in Dictyostelium

Seido Nagano & Shunsuke Sakurai


Physical Review E88, 062710(2013)

We propose a new cellular dynamics scheme for the spontaneous cAMP 
oscillations in Dictyostelium discoideum.Our scheme seamlessly integrates 
both receptor dynamics andG-protein dynamics into our previously developed 
cellular dynamics scheme. Extensive computer simulation studies based on 
our new cellular dynamics scheme were conducted in mutant cells to evaluate 
the molecular network. The validity of our proposed molecular network as well 
as the controversial PKA-dependent negative feedback mechanism was 
supported by our simulation studies. Spontaneous cAMP oscillations were not 
observed in a single mutant cell. However, multicellular states of various 
mutant cells consistently initiated spontaneous cAMP oscillations. Therefore, 
cell-to-cell coordination via the cAMP receptor is essential for the robust 
initiation of spontaneous cAMP oscillations.


Submitted by Seido Nagano [[log in to unmask]]]
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[End dictyNews, volume 40, number 2]