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–MATRIX JUNCTIONS
1081
TALIN
N
integrinbinding
domain
(A)
(B)
N
vinculin-binding sites
helices
1 to 12
tag attaches N-terminus
to glass slide
actinbinding
domain
folded talin helices 1 to 12
C-terminus attached
to magnetic bead
C
helix 12
magnetic
electrode
actin-binding
domain
domains are unfolded by stretching the protein (Figure 19–60). The N-terminal
end of talin binds integrin and the C-terminal end binds actin (see Figure 19–55);
thus, when actin filaments are pulled by myosin motors inside the cell, the resulting
tension stretches the talin rod, thereby exposing vinculin-binding sites. The
vinculin molecules then recruit and organize additional actin filaments. Tension
thereby increases the strength of the junction.
Summary
MBoC6 n19.207/19.61
Integrins are the principal cell-surface receptors used by animal cells to bind to the
extracellular matrix: they function as transmembrane linkers between the extracellular
matrix and the cytoskeleton. Most integrins connect to actin filaments, while
those at hemidesmosomes bind to intermediate filaments. Integrin molecules are
heterodimers, and the binding of extracellular matrix ligands or intracellular activator
proteins such as talin results in a dramatic conformational switch from an
inactive to an active state. This creates an allosteric coupling between binding to
matrix outside the cell and binding to the cytoskeleton inside it, allowing the integrin
to convey signals in both directions across the plasma membrane. Complex
assemblies of proteins become organized around the intracellular tails of activated
integrins, producing intracellular signals that can influence almost any aspect of
cell behavior, from proliferation and survival, as in the phenomenon of anchorage
dependence, to cell polarity and guidance of migration. Integrin-based cell–matrix
junctions are also capable of mechanotransduction: they can sense and respond to
mechanical forces acting across the junction.
force
as talin unfolds, helix 12 is
exposed and can bind to vinculin
vinculin
C
Figure 19–60 Talin is a tension sensor
at cell–matrix junctions. Tension
across cell–matrix junctions stimulates
the local recruitment of vinculin and
other actin-regulatory proteins, thereby
strengthening the junction’s attachment
to the cytoskeleton. The experiments
presented here tested the hypothesis that
tension is sensed by the talin adaptor
protein that links integrins to actin filaments
(see Figure 19–55). (A) The long, flexible,
C-terminal region of talin is divided into a
series of folded domains, some of which
contain vinculin-binding sites (dark green
lines) that are thought to be hidden and
therefore inaccessible. One domain near
the N-terminus, for example, comprises a
folded bundle of 12 α helices containing
five vinculin-binding sites. (B) This
experiment tested the hypothesis that
tension stretches the 12-helix domain,
thereby exposing vinculin-binding sites.
A fragment of talin containing this domain
was attached to an apparatus in which the
domain could be stretched, as shown here.
The fragment was labeled at its N-terminus
with a tag that sticks to the surface of a
glass slide on a microscope stage. The
C-terminal end of the fragment was bound
to a tiny magnetic bead, so the talin
fragment could be stretched using a small
magnetic electrode. The solution around
the protein contained fluorescently tagged
vinculin proteins. After the talin protein was
stretched, excess vinculin solution was
washed away, and the microscope was
used to determine if any fluorescent vinculin
proteins were bound to the talin protein.
In the absence of stretching (top), most
talin molecules did not bind vinculin. When
the protein was stretched (bottom), two or
three vinculin molecules were bound (only
one is shown here for clarity). (Adapted
from A. del Rio et al., Science 323:638–
641, 2009.)
THE PLANT CELL WALL
Each cell in a plant deposits, and is in turn completely enclosed by, an elaborate
extracellular matrix called the plant cell wall. It was the thick cell walls of cork, visible
in a primitive microscope, that in 1663 enabled Robert Hooke to distinguish
and name cells for the first time. The walls of neighboring plant cells, cemented