Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

954 Chapter 16: The Cytoskeleton
(A)
20 µm
(B)
actin and cofilin
actin
only
Maintenance of unidirectional motion by lamellipodia is thought to require
the cooperation and mechanical integration of several factors. Filament nucleation
is localized at the leading edge, with new actin filament growth occurring
primarily in that location to push the plasma membrane forward. Most filament
depolymerization occurs at sites located well behind the leading edge. Because
cofilin (see Figure 16–20) binds cooperatively and preferentially to actin filaments
containing ADP-actin (the D form), the new T-form filaments generated at the
leading edge should be resistant to depolymerization by cofilin (Figure 16–79).
As the filaments age and ATP hydrolysis proceeds, cofilin can efficiently disassemble
the older filaments. Thus, the delayed ATP hydrolysis by filamentous
actin is thought to provide the basis for a mechanism that maintains an efficient,
unidirectional treadmilling process in the lamellipodium (Figure 16–80); it also
explains the intracellular movement of MBoC6 bacterial m16.89/16.81
pathogens such as Listeria (see
Figure 16–25).
Figure 16–79 Cofilin in lamellipodia.
(A) A keratocyte with actin filaments
labeled in red by fluorescent phalloidin, and
cofilin labeled in green with a fluorescent
antibody. Although the dense actin
meshwork reaches all the way through the
lamellipodium, cofilin is not found at the
very leading edge. (B) Close-up view of
the region marked with the white rectangle
in (A). The actin filaments closest to the
leading edge, which are also the ones that
have formed most recently and that are
most likely to contain ATP-actin (rather than
ADP-actin), are generally not associated
with cofilin. (From T. Svitkina and G. Borisy,
J. Cell Biol. 145:1009–1026, 1999. With
permission from the authors.)
Myosin Contraction and Cell Adhesion Allow Cells to Pull
Themselves Forward
Forces generated by actin filament polymerization at the front of a migrating cell
are transmitted to the underlying substratum to drive cell motion. For the leading
capping
protein
cofilin
net filament
assembly at
leading edge
net filament
disassembly behind
leading edge
diffusion
of actin
monomers
Arp2/3
Figure 16–80 A model for protrusion
of the actin meshwork at the leading
edge. Two time points during advance of
the lamellipodium are illustrated, with newly
assembled structures at the later time
point shown in a lighter color. Nucleation
is mediated by the Arp 2/3 complex at
the front. Newly nucleated actin filaments
are attached to the sides of preexisting
filaments, primarily at a 70° angle.
Filaments elongate, pushing the plasma
membrane forward because of some
sort of anchorage of the array behind. At
a steady rate, actin filament plus ends
become capped. After newly polymerized
actin subunits hydrolyze their bound ATP in
the filament lattice, the filaments become
susceptible to depolymerization by cofilin.
This cycle causes a spatial separation
between net filament assembly at the
front and net filament disassembly at the
rear, so that the actin filament network as
a whole can move forward, even though
the individual filaments within it remain
stationary with respect to the substratum.
Not all of the actin disassembles, however,
and actin at the rear of the lamellipodium
contributes to subsequent steps of
migration together with myosin.