Essential Cell Biology 5th edition

578 CHAPTER 17 Cytoskeleton
basal cell of epidermis
(A)
40 µm
(B)
basal lamina
hemidesmosomes
(C)
defective keratin
filament network
Figure 17–6 A mutant form of keratin
makes skin more prone to blistering.
A mutant gene encoding a truncated
keratin protein was introduced into a
mouse. The defective protein assembles
with the normal keratins and thereby
disrupts the keratin filament network in
the skin. (A) Light micrograph of a cross
section of normal skin, which is resistant
to mechanical pressure. (B) Cross section
of skin from a mutant mouse showing the
formation of a blister, which results from the
rupturing of cells in the basal layer of the
mutant epidermis (short red arrow). (C) A
sketch of three cells in the basal layer of the
mutant epidermis. As indicated by the red
arrow, the cells rupture between the nucleus
and the hemidesmosomes that connect
the cells—via their keratin filaments—to
the underlying basal lamina. (From P.A.
Coulombe et al., J. Cell Biol. 115:1661–1674,
1991. With permission from The Rockefeller
University Press.)
Figure 17–7 Intermediate filaments
support and strengthen the nuclear
envelope. (A) Schematic cross section
through the nuclear envelope. The
intermediate filaments of the nuclear
lamina line the inner face of the nuclear
envelope and are thought to provide
attachment sites for the chromosomes.
(B) Electron micrograph of a portion
of the nuclear lamina from a frog egg.
The lamina is formed from a lattice of
intermediate filaments composed of
lamins. The nuclear lamina in other cell
types is not always as regularly organized
as the one shown here. (B, from U. Aebi
et al., Nature 323:560–564, 1986. With
permission from Macmillan Publishers Ltd.)
Defects in neurofilaments can also lead to disease. Neurofilaments are
intermediate filaments that are found along the axons of vertebrate neurons,
where they provide strength and stability to the long axons that
nerve ECB5 m16.69/17.06 cells use to transmit information. The neurodegenerative disease
amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease)
is associated with an abnormal accumulation of neurofilaments in the
cell bodies and axons of motor neurons. This accretion may precipitate
the axon degeneration and muscle weakness seen in these patients.
The Nuclear Envelope Is Supported by a Meshwork of
Intermediate Filaments
Whereas cytoplasmic intermediate filaments form ropelike structures, the
intermediate filaments lining and strengthening the inside surface of the
inner nuclear membrane are organized as a two-dimensional meshwork
(Figure 17–7). As mentioned earlier, the intermediate filaments that form
this tough nuclear lamina are constructed from a class of intermediate
filament proteins called lamins (not to be confused with laminin, which
is an extracellular matrix protein). The nuclear lamina disassembles and
re-forms at each cell division, when the nuclear envelope breaks down
during mitosis and then re-forms in each daughter cell (discussed in
Chapter 18).
The collapse and reassembly of the nuclear lamina is controlled by the
phosphorylation and dephosphorylation of the lamins. Phosphorylation
of lamins by protein kinases (discussed in Chapter 4) weakens the interactions
between the lamin tetramers and causes the filaments to fall
apart. Dephosphorylation by protein phosphatases at the end of mitosis
allows the lamins to reassemble (see Figure 18–30).
CYTOSOL
nuclear envelope
nuclear
lamina
nuclear
pore
NUCLEUS
chromatin
(A) (B) 1 µm