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

CELL POLARIZATION AND MIGRATION
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Figure 16–81 Contribution of myosin II to polarized cell motility.
(A) Myosin II bipolar filaments bind to actin filaments in the lamellipodial
meshwork and cause network contraction. The myosin-driven reorientation
of the actin filaments forms an actin bundle that recruits more myosin II
and helps generate the contractile forces required for retraction of the
trailing edge of the moving cell. (B) A fragment of the large lamellipodium
of a keratocyte can be separated from the main cell body either by surgery
with a micropipette or by treating the cell with certain drugs. Many of these
fragments continue to move rapidly, with the same overall cytoskeletal
organization as the intact keratocytes. Actin (blue) forms a protrusive
meshwork at the front of the fragment. Myosin II (pink) is gathered into
a band at the rear. (From A. Verkhovsky et al., Curr. Biol. 9:11–20, 1999.
With permission from Elsevier.)
actin
myosin
edge of a migrating cell to advance, protrusion of the membrane must be followed
by adhesion to the substratum at the front. Conversely, in order for the cell body
to follow, contraction must be coupled with de-adhesion at the rear of the cell.
The processes contributing to migration are therefore tightly regulated in space
and time, with actin polymerization, dynamic adhesions, and myosin contraction
being employed to coordinate movement. Myosin II operates in at least two ways
to assist cell migration. The first is by helping to connect the actin cytoskeleton to
the substratum through integrin-mediated adhesions. Forces generated by both
actin polymerization and myosin activity create tension at attachment sites, promoting
their maturation into focal adhesions, which are dynamic assemblies of
structural and signaling proteins that link the migrating cell to the extracellular
matrix (see Figure 19–59). A second mechanism involves bipolar myosin II filaments,
which associate with the actin filaments at the rear of the lamellipodium
and pull them into a new orientation—from nearly perpendicular to the leading
edge to almost parallel to the leading edge. This sarcomere-like contraction prevents
protrusion, and it pinches in the sides of the locomoting lamellipodium,
helping to gather in the sides of the cell as it moves forward (Figure 16–81).
Actin-mediated protrusions can only push the leading edge of the cell forward
if there are strong interactions between the actin network and the focal adhesions
that link the cell to the substrate. When these interactions are disengaged, polymerization
pressure at the leading edge and myosin-dependent contraction cause
the actin network to slip back, resulting in a phenomenon known as retrograde
flow (Figure 16–82).
The traction forces generated by locomoting cells exert a significant pull on the
substratum. By growing cells on a surface coated with tiny flexible posts, the force
exerted on the substratum can be calculated by measuring the deflection of each
post from its vertical position (Figure 16–83). In a living animal, most crawling
cells move across a semiflexible substratum made of extracellular matrix, which
can be deformed and rearranged by these cell forces. Conversely, mechanical tension
or stretching applied externally to a cell will cause it to assemble stress fibers
and focal adhesions, and become more contractile. Although poorly understood,
this two-way mechanical interaction between cells and their physical environment
is thought to help vertebrate tissues organize themselves.
(A)
(B)
MBoC6 m16.91/16.83
Cell Polarization Is Controlled by Members of the Rho Protein
Family
Cell migration requires long-distance communication and coordination between
one end of a cell and the other. During directed migration, it is important that the
front end of the cell remain structurally and functionally distinct from the back
end. In addition to driving local mechanical processes such as protrusion at the
front and retraction at the rear, the cytoskeleton is responsible for coordinating
cell shape, organization, and mechanical properties from one end of the cell to
the other, a distance that is typically tens of micrometers for animal cells.
In many cases, including but not limited to cell migration, large-scale cytoskeletal
coordination takes the form of the establishment of cell polarity, where
a cell builds different structures with distinct molecular components at the front