dictyNews
Electronic Edition
Volume 47, number 26
December 17, 2021
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Abstracts
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Extracellular Signalling Modulates Scar/WAVE Complex Activity
through Abi Phosphorylation.
Shashi Prakash Singh, Peter A. Thomason and Robert H. Insall
* Correspondence: [log in to unmask]
Cells, accepted
The lamellipodia and pseudopodia of migrating cells are produced
and maintained by the Scar/WAVE complex. Thus, actin-based cell
migration is largely controlled through regulation of Scar/WAVE.
Here, we report that the Abi subunit— but not Scar—is
phosphorylated in response to extracellular signalling in Dictyostelium
cells. Like Scar, Abi is phosphorylated after the complex has been
activated, implying that Abi phosphorylation modulates pseudopodia,
rather than causing new ones to be made. Consistent with this, Scar
complex mutants that cannot bind Rac are also not phosphorylated.
Several environmental cues also affect Abi phosphorylation—cell-
substrate adhesion promotes it and increased extracellular osmolarity
diminishes it. Both unphosphorylatable and phosphomimetic Abi
efficiently rescue the chemotaxis of Abi KO cells and pseudopodia
formation, confirming that Abi phosphorylation is not required for
activation or inactivation of the Scar/WAVE complex. However,
pseudopodia and Scar patches in the cells with unphosphorylatable
Abi protrude for longer, altering pseudopod dynamics and cell speed.
Dictyostelium, in which Scar and Abi are both unphosphorylatable, can
still form pseudopods, but migrate substantially faster. We conclude
that extracellular signals and environmental responses modulate cell
migration by tuning the behaviour of the Scar/WAVE complex after it
has been activated.
Submitted by Robert Insall [[log in to unmask]]
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Deletion of gmfA induces keratocyte-like migration in
Dictyostelium
Koushiro Fujimoto, Kentaro Nakano, Hidekazu Kuwayama and
Shigehiko Yumura
FEBS Open Bio
https://febs.onlinelibrary.wiley.com/doi/10.1002/2211-5463.13339
Glia maturation factor (GMF) has been established as an inactivating
fac- tor of the actin-related protein 2/3 (Arp2/3) complex, which
regulates actin assembly. Regulation of actin assembly and
reorganization is crucial for various cellular events, such as cell
migration, cell division, and develop- ment. Here, to examine the roles
of ADF-H domain-containing protein (also known as glia maturation
factor; GmfA), the product of a single GMF homologous gene in
Dictyostelium, gmfA-null cells were generated. They had moderate
defects in cell growth and cytokinesis. Interestingly, they showed a
keratocyte-like fan shape with a broader pseudopod, where Arp3
accumulated at higher levels than in wild-type cells. They migrated
with higher persistence, but their velocities were comparable to those
of wild-type cells. The polar pseudopods during cell division were also
broader than those in wild-type cells. However, GmfA did not localize
at the pseudopods in migrating cells or the polar pseudopods in dividing
cells. Adhesions of mutant cells to the substratum were much stronger
than that of wild-type cells. Although the mutant cells showed chemotaxis
compara- ble to that of wild-type cells, they formed disconnected streams
during the aggregation stage; however, they finally formed normal fruiting
bodies. These results suggest that GmfA plays a crucial role in cell
migration.
Submitted by Shigehiko Yumura [[log in to unmask]]
———————————————————————————————
A systems approach to investigate GPCR-mediated Ras signaling
network in chemoattractant sensing
Xuehua Xu1, Wei Quan1, Fengkai Zhang2 and Tian Jin1
1Chemotaxis Signal Section, Laboratory of Immunogenetics, National
Institute of Allergy and Infectious Diseases, National Institutes of Health,
Rockville, MD 20852, USA
2Computational Biology Section, Laboratory of Immune System Biology,
National Institute of Allergy and Infectious Diseases, National Institutes
of Health, Bethesda, MD, USA
Correspondence to: Tian Jin ([log in to unmask])
Molecular Biology of Cell, in press
A GPCR-mediated signaling network enables a chemotactic cell to generate
adaptative Ras signaling in response to a large range of concentrations of a
chemoattractant. To explore potential regulatory mechanisms of GPCR-
controlled Ras signaling in chemosensing, we applied a software package,
Simmune, to construct detailed spatiotemporal models simulating responses
of the cAR1-mediated Ras signaling network. We first determined dynamics
of G-protein activation and Ras signaling in Dictyostelium cells in response to
cAMP stimulations using live cell imaging and then constructed computation
models by incorporating potential mechanisms. Using simulations, we validated
the dynamics of signaling events and predicted the dynamic profiles of those
events in the cAR1-mediated Ras signaling networks with defective Ras
inhibitory mechanisms, such as without RasGAP, with RasGAP overexpression,
or RasGAP hyperactivation. We described a method of using Simmune to
construct spatiotemporal models of a signaling network and run computational
simulations without writing mathematical equations. This approach will help
biologists to develop and analyze computational models that parallel live-cell
experiments.
Submitted by Xuehua Xu [[log in to unmask]]
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[End dictyNews, volume 47, number 26]
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