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The Cell: Basic Structure and Function
term. Aberrant centrosomes are a hallmark of chromosomally
instable cancer cells. Because of aberrant formation of the
mitotic spindle apparatus, these cells acquire more and more
chromosomal aberrations.
Two classes of substances can interfere with the microtubular
network: Colchicine prevents the polymerization of microtu-
bules, while paclitaxel interferes with their depolymerization.
In a living cell, the microtubular network is continuously
polymerized and depolymerized. Therefore, both agents lead to
a non-functional spindle apparatus abrogating the cell division
and are used as cytotoxins in cancer therapy.
Cell Membrane, Receptors, and Signal
Transduction
The basic structure of the cell membrane is a semi-permeable
lipid bilayer built from phospholipids, glycolipids, and steroids
that contains various proteins floating on one side of or reaching
through the complete membrane. The lipid bilayer has a gauge
of 6 to 10 nm and is barely visible in light microscopy. The cell
membrane separates all cellular components from the environ-
ment and it assures the spatial and functional entity of a single
cell. It allows the cell to persist in environments that would be
harmful to the cellular components, such as extreme pH condi-
tions and ion concentrations different from the cytoplasm. The
cell membrane controls what is going into and out of a cell;
thereby it regulates the import of nutrients and the export of cel-
lular products. The transport is organized by passive (transport
via a gradient that does not require energy) and active (transport
against a gradient that requires energy) protein channels.
There are different types of membrane proteins. Peripheral
membrane proteins only temporarily adhere to the respective
cell membrane; they usually interact with integral membrane
proteins. Many regulatory subunits of ion channel and trans-
membrane receptors, as well as enzymes and hormones, are
peripheral membrane proteins. In contrast, integral membrane
proteins are permanently attached to the membrane. Trans-
membrane proteins are integral proteins that span both lipid
layers; they must contain a hydrophobic part that is placed in
the lipid section and hydrophilic intra- and extracellular parts.
Typical representatives are ion channels, proton pumps, and
G-protein coupled receptors. Lipid-anchored proteins are cova-
lently linked to lipids in the cell membrane; the most common
are G-proteins.
The communication of a cell with the environment (i.e. other
cells or the extracellular matrix) is mediated by a wide varia-
tion of interacting molecules, usually designated as receptors.
The functional principle of receptors is based on the key-lock
principle; i.e. a specific receptor requires the binding of a specific
ligand (either cell based or freely circulating) to be activated.
The transfer of information between cells may be mediated
by two different classes of receptors located in the cell mem-
brane: Ionotropic receptors are based on specific ion channels
that change the electric potential of cells upon activation (Fig.
1.6A). Non-ionotropic receptors have no pores, but are based
on transmembrane proteins that stimulate intracellular proteins
linked to the receptors and thereby modulate intracellular signal
cascades.
The two most important non-ionotropic receptor types are
G-protein coupled receptors and tyrosine kinase receptors.
G-protein coupled receptors consist of seven transmembrane
domains, an extracellular receptor region, and an intracellular
part that binds the G-protein (Fig. 1.6B). Upon activation by
an outside signal, the receptor changes its conformation and
releases the G-protein in a not yet fully resolved mechanism.
G-proteins, short for guanine nucleotide binding proteins, are
the most important proteins involved in second messenger
cascades, responsible for many central nervous (vision, olfac-
tory system, neurotransmitters) and immune system func-
tions. Receptor tyrosine kinases activate downstream targets
by adding phosphate groups to intracellular proteins (Fig.
1.6C). They are frequently promoting cell growth and cell
division (e.g. receptors for insulin-like growth factor, epider-
mal growth factor, EGF). Consequently, many malignant pro-
cesses are linked to aberrations of G-protein coupled receptors
and especially tyrosine kinase receptors. In about 25% of the
breast cancers, a subtype of EGF receptors (ErbB2/Her2neu) is
overexpressed, which leads to increased signaling of the EGF
pathway, resulting in increased cell proliferation. Meanwhile,
inactivating antibodies directed against Her2neu are success-
fully used in breast cancer therapy. Similarly, cetuximab is a
monoclonal antibody downregulating ErbBl signaling that
has been approved for special types of colorectal cancer.
Cell Junctions
As complex organisms are built from billions of cells, the cell-
to-cell contact is a very important parameter. Depending on the
organ or the function of a tissue, cell contacts establish adherence
of functionally connected cells, build a barrier against a lumen,
and are involved in intercellular communication (Fig. 1.5).
Adherence is based mainly on spot desmosomes (macula
adhaerens) consisting of keratin filaments that connect the
cytoskeleton of individual cells. A different form of adherence
is the adhesion belt (zonula adherens) that connects the apical
part of an epithelial cell to another epithelial cell. Hemidesmo-
somes are located at the basal pole of the cell and attach the cell
to the basal membrane.
Tight junctions (zonula occludens) build an impermeable
barrier between cells and are typical for structures that have a
lumen.
Gap junctions are required for communication; small inor-
ganic molecules and electric signals are exchanged via 1.5-nm
pores in the cell membrane. Gap junctions can be quickly estab-
lished from precursors floating in plasma membrane.
The terminal bar describes a light microscopic structure that
represents the sum of the adhesion belt and actin filament bun-
dles as well as other protein filaments at the apical end of a cell.
In general, malignancy causes loss of cell-to-cell adherence.
It has been shown that the cell adhesion molecule E-cadherin is
lost during the formation of some epithelial cancers. The loss of
E-cadherin is frequently accompanied by an overexpression of
other cadherins, an effect called the "cadherin switch." Besides
the cell adhesion, signal transduction pathways are altered,
inducing malignant transformation of the respective cell.
Cell Growth and Division
In mammalian organisms, some cells are created early in embry-
ogenesis and remain unchanged throughout the whole life
(e.g. lens of eyes, cells of CNS, heart muscle cells, auditory cells
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