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

894 Chapter 16: The Cytoskeleton
them produce important differences in the stability and mechanical properties
of each type of filament. Whereas covalent linkages between their subunits hold
together the backbones of many biological polymers—including DNA, RNA, and
proteins—it is weak noncovalent interactions that hold together the three types of
cytoskeletal polymers. Consequently, their assembly and disassembly can occur
rapidly, without covalent bonds being formed or broken.
The subunits of actin filaments and microtubules are asymmetrical and bind
to one another head-to-tail so that they all point in one direction. This subunit
polarity gives the filaments structural polarity along their length, and makes the
two ends of each polymer behave differently. In addition, actin and tubulin subunits
are both enzymes that catalyze the hydrolysis of a nucleoside triphosphate—
ATP and GTP, respectively. As we discuss later, the energy derived from nucleotide
hydrolysis enables the filaments to remodel rapidly. By controlling when and
where actin and microtubules assemble, the cell harnesses the polar and dynamic
properties of these filaments to generate force in a specific direction, to move the
leading edge of a migrating cell forward, for example, or to pull chromosomes
apart during cell division. In contrast, the subunits of intermediate filaments are
symmetrical, and thus do not form polarized filaments with two different ends.
Intermediate filament subunits also do not catalyze the hydrolysis of nucleotides.
Nevertheless, intermediate filaments can be disassembled rapidly when required.
In mitosis , for example, kinases phosphorylate the subunits, leading to their dissociation.
Cytoskeletal filaments in living cells are not built by simply stringing subunits
together in single file. A thousand tubulin subunits lined up end-to-end,
for example, would span the diameter of a small eukaryotic cell, but a filament
formed in this way would lack the strength to avoid breakage by ambient thermal
energy, unless each subunit in the filament was bound extremely tightly to its two
neighbors. Such tight binding would limit the rate at which the filaments could
disassemble, making the cytoskeleton a static and less useful structure. To provide
both strength and adaptability, microtubules are built of 13 protofilaments—linear
strings of subunits joined end-to-end—that associate with one another laterally
to form a hollow cylinder. The addition or loss of a subunit at the end of one
protofilament makes or breaks a small number of bonds. In contrast, loss of a subunit
from the middle of the filament requires breaking many more bonds, while
breaking it in two requires breaking bonds in multiple protofilaments all at the
same time (Figure 16–5). The greater energy required to break multiple noncovalent
bonds simultaneously allows microtubules to resist thermal breakage, while
allowing rapid subunit addition and loss at the filament ends. Helical actin filaments
are much thinner and therefore require much less energy to break. However,
multiple actin filaments are often bundled together inside cells, providing
mechanical strength, while allowing dynamic behavior of filament ends.
As with other specific protein–protein interactions, many hydrophobic interactions
and noncovalent bonds hold the subunits in a cytoskeletal filament together
(see Figure 3–4). The locations and types of subunit–subunit contacts differ for
the different filaments. Intermediate filaments, for example, assemble by forming
strong lateral contacts between α-helical coiled-coils, which extend over most of
the length of each elongated fibrous subunit. Because the individual subunits are
staggered in the filament, intermediate filaments form strong, ropelike structures
that tolerate stretching and bending to a greater extent than do either actin filaments
or microtubules (Figure 16–6).
Accessory Proteins and Motors Regulate Cytoskeletal Filaments
The cell regulates the length and stability of its cytoskeletal filaments, as well as
their number and geometry. It does so largely by regulating their attachments
to one another and to other components of the cell, so that the filaments can
form a wide variety of higher-order structures. Direct covalent modification of
the filament subunits regulates some filament properties, but most of the regulation
is performed by hundreds of accessory proteins that determine the spatial