dictyNews
Electronic Edition
Volume 35, number 7
September 17, 2010

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Abstracts
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Peter J.M. Van Haastert

A model for a correlated random walk based on the ordered
extension of pseudopodia

Department of Cell Biochemistry, University of Groningen,
Kerklaan 30, 9751 NN Haren, the Netherlands


PLoS Comp. Biol., in press

Cell migration in the absence of external cues is well described by a
correlated random walk. Most single cells move by extending protrusions
called pseudopodia. To deduce how cells walk, we have analyzed the
formation of pseudopodia by Dictyostelium cells. We have observed
that the formation of pseudopodia is highly ordered with two types of
pseudopodia: First, de novo formation of pseudopodia at random
positions on the cell body, and therefore in random directions. Second,
pseudopod splitting near the tip of the current pseudopod in alternating
right/left directions, leading to a persistent zig-zag trajectory.  
Here we
analyzed the probability frequency distributions of the angles between
pseudopodia and used this information to design a stochastic model for
cell movement. Monte Carlo simulations show that the critical elements
are the ratio of persistent splitting pseudopodia relative to random de
novo pseudopodia, the Left/Right alternation, the angle between
pseudopodia and the variance of this angle. Experiments confirm
predictions of the model, showing reduced persistence in mutants
that are defective in pseudopod splitting and in mutants with an
irregular cell surface.


Submitted by  Peter Van Haastert [[log in to unmask]]
--------------------------------------------------------------------------------


Peter J.M. Van Haastert

A stochastic model for chemotaxis based on the ordered extension of
pseudopods

Department of Cell Biochemistry, University of Groningen,
Kerklaan 30, 9751 NN Haren, The Netherlands


Biophysical Journal, in press

Many amoeboid cells move by extending pseudopods. Here we
present a new stochastic model for chemotaxis that is based on
pseudopod extensions by Dictyostelium cells. In the absence of
external cues, pseudopod extension is highly ordered with two types
of pseudopods: de novo formation of a pseudopod at the cell body in
random directions, and alternating right/left splitting of an existing
pseudopod that leads to a persistent zig-zag trajectory. We measured
the directional probabilities of the extension of splitting and de novo
pseudopods in chemoattractant gradients with different steepness.
Very shallow cAMP gradients can bias the direction of splitting
pseudopods, but the bias is not perfect. Orientation of de novo
pseudopods require much steeper cAMP gradients and can be more
precise. These measured probabilities of pseudopod directions were
used to obtain an analytical model for chemotaxis of cell populations.
Measured chemotaxis of wild type cells and mutants with specific
defects in these stochastic pseudopod properties are similar to
predictions of the model. These results show that combining splitting
and de novo pseudopods is a very effective way for cells to obtain
very high sensitivity to stable gradient and still be responsive to
changes in the direction of the gradient.


Submitted by  Peter Van Haastert [[log in to unmask]]
--------------------------------------------------------------------------------


Peter J.M. Van Haastert

Chemotaxis: insights from the extending pseudopod

Department of Cell Biochemistry, University of Groningen,
Kerklaan 30, 9751 NN Haren, the Netherlands


J. Cell Sci., in press

Chemotaxis is one of the most fascinating processes in cell biology.
Shallow gradients of chemoattractant direct the movement of cells,
and an intricate network of signalling pathways somehow instructs
the movement apparatus to induce pseudopods in the direction of
these gradients. Exciting new experiments have approached
chemotaxis from the perspective of the extending pseudopod.
These recent studies have revealed that, in the absence of external
cues, cells use endogenous signals for the highly ordered extension
of pseudopods, which appear mainly as alternating right and left
splits. In addition, chemoattractants activate other signalling
molecules that induce a positional bias of this basal system, such
that the extending pseudopods are oriented towards the gradient.
In this Commentary, I review the findings of these recent experiments,
which together provide a new view of cell movement and chemotaxis.



Submitted by  Peter Van Haastert [[log in to unmask]]
------------------------------------------------------------------------------


Regulation of Hip1r by epsin controls the temporal and spatial
coupling of actin filaments to clathrin-coated pits

Rebecca J. Brady (1), Cynthia K. Damer (2), John E. Heuser (3)
and Theresa J. O’Halloran (1)

(1) Department of Molecular Cell and Developmental Biology,
University of Texas at Austin, Austin, TX 78712
(2) Department of Biology, Central Michigan University,
Mount Pleasant, MI 48858
(3) Department of Cell Biology and Biophysics,
Washington University, St. Louis, MO 63130


Journal of Cell Science, in press

Recently, it has become clear that the actin cytoskeleton is involved
in clathrin-mediated endocytosis. During clathrin-mediated endocytosis,
clathrin triskelions and adaptor proteins assemble into lattices,  
forming
clathrin-coated pits. These coated pits invaginate and detach from the
membrane, a process that requires dynamic actin polymerization. We
found an unexpected role for the clathrin adaptor epsin in regulating
actin dynamics during this late stage of coated vesicle formation.  In
Dictyostelium cells, epsin is required for both the membrane
recruitment and phosphorylation of the actin- and clathrin-binding
protein Hip1r. Epsin-null and Hip1r-null cells exhibit deficiencies in  
the
timing and organization of actin filaments at clathrin-coated pits.
Consequently, clathrin structures persist on the membranes of epsin
and Hip1r mutants and the internalization of clathrin structures is  
delayed.
We conclude that epsin works with Hip1r to regulate actin dynamics by
controlling the spatial and temporal coupling of actin filaments to  
clathrin
coated pits. Specific residues in the ENTH domain of epsin that are
required for the membrane recruitment and phosphorylation of Hip1r
are also required for normal actin and clathrin dynamics at the plasma
membrane. We propose that epsin promotes the membrane recruitment
and phosphorylation of Hip1r, which in turn regulates actin  
polymerization
at clathrin-coated pits.


Submitted by Terry O’Halloran [[log in to unmask]]
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[End dictyNews, volume 35, number 7]