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

948 Chapter 16: The Cytoskeleton
(A)
(B)
100 nm
(C)
microtubules
neurofilaments
250 nm
The vimentin-like filaments are a third family of intermediate filaments.
Desmin, a member of this family, is expressed in skeletal, cardiac, and smooth
muscle, where it forms a scaffold around the Z disc of the sarcomere (see Figure
16–34). Mice lacking desmin show normal initial muscle development, but adults
have various muscle-cell abnormalities, including misaligned muscle fibers. In
humans, mutations in desmin are associated with various forms of muscular dystrophy
and cardiac myopathy, illustrating the important MBoC6 m16.22/16.72
role of desmin in stabilizing
muscle fibers.
Besides their well-established role in maintaining the mechanical stability
of the nucleus, it is becoming increasingly evident that one class of lamins, the
A-type, together with many proteins of the nuclear envelope, are scaffolds for proteins
that control myriad cellular processes including transcription, chromatin
organization, and signal transduction. The majority of laminopathies are associated
with mutant versions of lamin A and include tissue-specific diseases. Skeletal
and cardiac abnormalities might be explained by a weakened nuclear envelope
leading to cell damage and death, but laminopathies are also thought to arise
from pathogenic and tissue-specific alterations in gene expression.
Linker Proteins Connect Cytoskeletal Filaments and Bridge the
Nuclear Envelope
The intermediate filament network is linked to the rest of the cytoskeleton by
members of a family of proteins called plakins. Plakins are large and modular,
containing multiple domains that connect cytoskeletal filaments to each other
and to junctional complexes. Plectin is a particularly interesting example. In addition
to bundling intermediate filaments, it links the intermediate filaments to
microtubules, actin filament bundles, and filaments of the motor protein myosin
II; it also helps attach intermediate filament bundles to adhesive structures at the
plasma membrane (Figure 16–71).
Plectin and other plakins can interact with protein complexes that connect
the cytoskeleton to the nuclear interior. These complexes consist of SUN proteins
Figure 16–70 Two types of intermediate
filaments in cells of the nervous system.
(A) Freeze-etch electron microscopic
image of neurofilaments in a nerve cell
axon, showing the extensive crosslinking
through protein cross-bridges—an
arrangement believed to give this long cell
process great tensile strength. The crossbridges
are formed by the long, nonhelical
extensions at the C-terminus of the largest
neurofilament protein (NF-H). (B) Freezeetch
image of glial filaments in glial cells,
showing that these intermediate filaments
are smooth and have few cross-bridges.
(C) Conventional transmission electron
micrograph of a cross section of an axon
showing the regular side-to-side spacing
of the neurofilaments, which greatly
outnumber the microtubules.
(A and B, courtesy of Nobutaka Hirokawa;
C, courtesy of John Hopkins.)
0.5 µm
Figure 16–71 Plectin cross-linking of
diverse cytoskeletal elements. Plectin
(green) is seen here making crosslinks
from intermediate filaments (blue)
to microtubules (red). In this electron
micrograph, the dots (yellow) are gold
particles linked to anti-plectin antibodies.
The entire actin filament network was
removed to reveal these proteins. (From
T.M. Svitkina et al., J. Cell Biol. 135:991–
1007, 1996. With permission from The
Rockefeller University Press.)