The Cytoskeleton
Besides its organelles, the
cytoplasm contains a network of microtubules, microfilaments, intermediate filaments,
and thick filaments (Fig. 4.6). Because they control cell shape and movement,
these structures are a major component of the structural elements called the cytoskeleton,
which participates in the
movement of entire cells.
Microtubules
Microtubules are formed from
protein subunits called tubulin. They are long, stiff, hollow,
cylindrical structures, 25 nm in outer diameter with a lumen 15 nm in diameter.
Each microtubule consists of parallel protofilaments, each composed of α- and
β-tubulin dimers. Microtubules are dynamic structures that can rapidly
disassemble in one location and reassemble in another. During the reassembly
process the tubulin dimers polymerize in an end-to-end fashion to form
protofilaments. As a result of the polymerization process, each microtubule
possesses a nongrowing “minus” end and a rapidly growing “plus” end. During the
disassembly process, the tubulin dimers dissociate from the protofilaments and
form a pool of free tubulin in the cytoplasm. This pool is used in the polymerization
process for reassembly of the protofilaments.
Microtubules function in many ways,
including the development and maintenance of cell form. They participate in
intracellular transport mechanisms, including axoplasmic transport in neurons
and melanin dispersion in pigment cells of the skin. Other functions include
formation of the basic structure for several complex cytoplasmic organelles,
including the centrioles, basal bodies, cilia, and flagella (Fig. 4.7).
The plant alkaloid colchicine binds
to tubulin molecules and prevents the assembly of microtubules. This compound
stops cell mitosis by interfering with formation of the mitotic spindle and is
often used for cytogenetic (chromosome) studies. It is also used in treating
gout to prevent migration of neutrophils and to lower their ability to respond
to urate crystals in the tissues. The
vinca alkaloid drugs (e.g.,vinblastine and vincristine), which are
sometimes used in the treatment of cancer, also bind to microtubules and
inhibit formation of the mitotic spindle, which is essential for cell
proliferation.
Centrioles and Basal Bodies. Centrioles and
basal bodies are structurally
identical organelles composed of highly organized microtubules. Internally,
centrioles and basal bodies have an amorphous central core surrounded by
clusters formed of triplet sets of microtubules.
Centrioles are small, cylindrical
structures composed of an array of highly organized microtubules. Usually they
are paired structures, arranged perpendicular to each other. In dividing cells,
the two cylindrical centrioles are initially found in the vicinity of the Golgi
apparatus in a region of the cell called the centrosome. During cell
division, centrioles form the mitotic spindle that aids in the separation and
movement of the chromosomes.
Basal bodies are more numerous than
centrioles and are found near the cell membrane in association with cilia and
flagella. They are responsible for the formation of the highly organized core of microtubules found in cilia
and flagella.
Cilia and Flagella. Cilia and flagella are microtubule-filled
cellular extensions whose enclosing
membrane is continuous with the cell membrane. Ciliated cells typically possess
a large number of cilia, whereas flagellated cells have only one flagellum. In
humans, the spermatozoa are the only cell type with flagella. Cilia are found
on the apical (luminal) surfaces of many epithelial linings, including the
nasal sinuses and bronchi in the upper respiratory system. They also play a
prominent role in sensory tissues such as the photoreceptor proteins in the
eye, the odorant receptors of the olfactory epithelium, and the kinocilium on
the hair cells in the inner ear. Cilia also act in sensory roles at critical
stages of embryonic development, and they are essential for the normal
functioning of many tissues, including the kidney, during postnatal life.
Recent research has linked the pathogenesis of a condition called polycystic
kidney disease to a genetic defect in the cilia of the renal tubular cells.
A motile cilium contains nine sets
of doublet microtubules that form
a hollow cylinder surrounding a central pair of singlet microtubules. The outer
doublet microtubules contain ATP motor–driven complexes that cause the adjacent
microtubule doublets to slide past each other. All of these microtubules and
their associated proteins are anchored to a basal body that is
responsible for the formation of a core structure called the axoneme. The
axoneme serves as the internal framework that sup- ports the cilium and
provides a structure on which mechanical movement is generated. Recent evidence
suggests that not all cilia contain this internal structure, and some may be
missing the central pair of microtubules. Cilia lacking the central core of
microtubules are often called primary cilia and are immotile.
Cilia and flagella are assembled
through a process called intraflagellar transport, during which large
protein complexes are transported along the ciliary microtubules from the basal
body to the ciliary tip and then back to the basal body. These protein
complexes are thought to carry ciliary precursors from their site of synthesis
in the cytoplasm to their site of assembly at the tip of the cilium. Genetic
defects can result in improper ciliary assembly and, as a result, the cilia may
be nonfunctional. One of these disorders, the immotile cilia syndrome, impairs
sperm motility, causing male sterility while also immobilizing the cilia of the
respiratory tract, thus interfering with clearance of inhaled bacteria, leading
to a chronic lung disease called bronchiectasis. Kartagener syndrome is
an example of immotile cilia syndrome and involves diffuse bronchiolitis, sinus
aplasia, and situs inversus totalis, which is a reversal of the thorax and
abdomen organs.
Microfilaments
Microfilaments are thin, threadlike
cytoplasmic structures. Three classes of microfilaments exist:
1.
Thin
microfilaments, which are equivalent to the thin actin filaments in muscle
2.
Intermediate
filaments, which are a heterogeneous group of filaments with diameter sizes
between those of the thick and thin filaments
3.
Thick
myosin filaments, which are present in muscle cells, but may also exist temporarily in other cells.
Muscle contraction depends on the interaction between the thin actin filaments and thick myosin filaments.
Microfilaments are present in the superficial zone of the cytoplasm in most
cells. Contractile activities involving the microfilaments and associated thick
myosin filaments contribute to the movement of the cytoplasm and cell membrane
during endocytosis and exocytosis. Microfilaments are also present in the
microvilli of the intestine. The intermediate filaments assist in supporting
and maintaining the asymmetric shape of cells. Examples of intermediate
filaments are the keratin filaments that are found anchored to the cell
membrane of epidermal keratinocytes of the skin and the glial filaments that
are found in astrocytes and other glial cells of the nervous system. The neurofibrillary
tangle found in the brain in Alzheimer disease contains
microtubule-associated proteins and neurofilaments, evidence of a disrupted
neuronal cytoskeleton.
