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dictyNews Volume 29 Number 09
dictyNews
Electronic Edition
Volume 29, number 9
September 28, 2007
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.
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Abstracts
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Chemotaxis: Navigating by Multiple Signaling Pathways
Peter J. M. Van Haastert and Douwe M. Veltman
Science’s STKE, pe40
During chemotaxis, phosphatidylinositol 3,4,5-trisphosphate (PIP3)
accumulates at the leading edge of a eukaryotic cell, where it induces the
formation of pseudopodia. PIP3 has been suggested to be the compass of cells
navigating in gradients of signaling molecules. Recent observations suggest
that chemotaxis is more complex than previously anticipated. Complete
inhibition of all PIP3 signaling has little effect, and alternative pathways
have been identified. In addition, selective pseudopod growth and retraction
are more important in directing cell movement than is the place where new
pseudopodia are formed.
Submitted by: Peter Van Haastert [p.j.m.van.haastert@rug.nl]
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PLC regulation of PI(3,4,5)P3-mediated chemotaxis
Arjan Kortholt*, Jason King*, Ineke Keizer-Gunnink, Adrian Harwood and
Peter J.M. Van Haastert
* these authors contributed equally to this work
Department of Molecular Cell Biology, University of Groningen, Kerklaan 30,
9751NN Haren, the Netherlands
School of Biosciences, Cardiff University, Museum Avenue, Cardiff,
UK. CF10 3US
Molecular Biology of the Cell, in press
Generation of a PI(3,4,5)P3 gradient within the plasma membrane is important
for cell polarization and chemotaxis in many eukaryotic cells. The gradient
is produced by the combined activity of PI3K to increase PI(3,4,5)P3 on the
membrane nearest the polarizing signal and PI(3,4,5)P3 dephosphorylation by
PTEN elsewhere. Common to both of these enzymes is the lipid PI(4,5)P2,
which is not only the substrate of PI3K and product of PTEN, but is also
important for membrane binding of PTEN. Consequently, regulation of PLC
activity, which hydrolyses PI(4,5)P2, could have important consequences
for PI(3,4,5)P3 localization. We investigate the role of PLC in PI(3,4,5)P3
mediated chemotaxis in Dictyostelium. plc-null cells are resistant to the
PI3K inhibitor LY294002 and produce little PI(3,4,5)P3 after cAMP
stimulation, as monitored by the PI(3,4,5)P3-specific PH-domain of CRAC
(PHCRACGFP). In contrast, PLC overexpression elevates PI(3,4,5)P3 and
impairs chemotaxis in a similar way to loss of pten. PI3K localisation
at the leading edge of plc-null cells is unaltered, but dissociation of
PTEN from the membrane is strongly reduced in both gradient and uniform
stimulation with cAMP. These results indicate that local activation of
PLC can control PTEN localization and suggest a novel mechanism to
regulate the internal PI(3,4,5)P3 gradient.
Submitted by: Peter Van Haastert [p.j.m.van.haastert@rug.nl]
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[End dictyNews, volume 29, number 9]
