Essential Cell Biology 5th edition

Intermediate Filaments
579
Figure 17–8 Defects in a nuclear lamin can cause a rare class of
premature aging disorders called progeria. (A) In a normal cell,
the protein lamin A (green) is assembled into a uniform nuclear
lamina inside the nuclear envelope. (B) In a cell with a lamin A
mutant that is found in patients with progeria, the nuclear lamina is
defective, resulting in structural defects in the nuclear envelope.
(C) Children with progeria begin to show features of advanced
aging early in life. (A and B, from P. Taimen et al., Proc. Natl Acad.
Sci. USA 106:20788–20793, 2009. With permission from National
Academy of Sciences; C, courtesy of The Progeria Research
Foundation, www.progeriaresearch.org.)
(A)
(B)
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Defects in a particular nuclear lamin are associated with certain types
of progeria—rare disorders that cause affected individuals to age prematurely.
Children with progeria have wrinkled skin, lose their teeth and hair,
and often develop severe cardiovascular disease by the time they reach
their teens (Figure 17–8). How the loss of a nuclear lamin could lead to
this devastating condition is not yet clear, but it may be that the resulting
nuclear instability leads to impaired cell division, increased cell death,
a diminished capacity for tissue repair, or some combination of these.
Because the nuclear lamina also helps properly position chromosomes,
defects in lamins might also lead to altered chromosome movement and,
ultimately, changes in gene expression.
Linker Proteins Connect Cytoskeletal Filaments and
Bridge the Nuclear Envelope
Many intermediate filaments are further stabilized and reinforced by
accessory proteins, such as plectin, that cross-link the filaments into
bundles and connect them to microtubules, to actin filaments, and to
adhesive structures in desmosomes (Figure 17–9). Mutations in the gene
for plectin cause a devastating human disease that combines features
of epidermolysis bullosa simplex (caused by disruption of skin keratin),
muscular dystrophy (caused by disruption of intermediate filaments in
muscle), and neurodegeneration (caused by disruption of neurofilaments).
Mice lacking a functional plectin gene die within a few days of
birth, with blistered skin and abnormal skeletal and heart muscle. Thus,
although plectin may not be necessary for the initial formation of intermediate
filaments, its cross-linking action is required to provide cells
with the strength they need to withstand mechanical stress.
Plectin and other proteins also interact with protein complexes that link
the cytoplasmic cytoskeleton to structures in the nuclear interior, including
chromosomes and the nuclear lamina (Figure 17–10). These bridges,
which span the nuclear envelope, mechanically couple the nucleus to
the cytoskeleton, and they are involved in many processes, including the
movement and positioning of the nucleus within the cell interior and the
overall organization of the cytoskeleton.
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(C)
QUESTION 17–1
Which of the following types of cells
would you expect to contain a high
density of intermediate filaments
in their cytoplasm? Explain your
answers.
A. Amoeba proteus (a free-living
amoeba)
B. Skin epithelial cell
C. Smooth muscle cell in the
digestive tract
D. Escherichia ECB5 e17.09/17.08 coli
E. Nerve cell in the spinal cord
F. Sperm cell
G. Plant cell
Figure 17–9 Plectin aids in the bundling
of intermediate filaments and links
these filaments to other cytoskeletal
protein networks. In this scanning
electron micrograph of the cytoskeletal
protein network from cultured fibroblasts,
the actin filaments have been removed,
and the plectin, intermediate filaments,
and microtubules have been artificially
colored. Note how the plectin (orange)
links an intermediate filament (blue) to
microtubules (green). The yellow dots are
gold particles linked to antibodies that
recognize plectin. (From T.M. Svitkina,
A.B. Verkhovsky, and G.G. Borisy, J. Cell
Biol. 135:991–1007, 1996. With permission
from The Rockefeller University Press.)