Essential Cell Biology 5th edition

Control of Cell Numbers and Cell Size
645
Figure 18−43 Extracellular growth factors increase the synthesis
and decrease the degradation of macromolecules. Binding of a
growth factor to a receptor tyrosine kinase (RTK, a class of cell-surface
receptor described in Chapter 16) initiates an intracellular signaling
pathway that leads to activation of a protein kinase called Tor, which
acts through multiple targets to stimulate protein synthesis and inhibit
protein degradation (see also Figure 16−34). This action leads to a net
increase in macromolecules and thereby cell growth.
growth factor
P
P
plasma
membrane
activated RTK
Like most survival factors and mitogens, most extracellular growth factors
bind to cell-surface receptors that activate intracellular signaling
pathways. These pathways lead to the accumulation of proteins and other
macromolecules. Growth factors both increase the rate of synthesis of
these molecules and decrease their rate of degradation (Figure 18−43).
Some extracellular signal proteins, including PDGF, can act as both
growth factors and mitogens, stimulating both cell growth and progression
through the cell cycle. Such proteins help ensure that cells maintain
their appropriate size as they proliferate.
Compared to cell division, there has been surprisingly little study of how
cell size is controlled in animals. As a result, it remains a mystery how
different cell types in the same animal grow to be so different in size
(Figure 18−44).
Some Extracellular Signal Proteins Inhibit Cell Survival,
Division, or Growth
The extracellular signal proteins that promote survival, growth, and
cell division act positively to increase the size of organs and organisms.
Some extracellular signal proteins, however, act to oppose these positive
regulators and thereby inhibit tissue growth. Myostatin, for example, is a
secreted signal protein that normally inhibits the growth and proliferation
of the precursor cells (myoblasts) that fuse to form skeletal muscle cells
during mammalian development. When the gene that encodes myostatin
is deleted in mice, their muscles grow to be several times larger than normal,
because both the number and the size of muscle cells is increased.
Remarkably, two breeds of cattle that were bred for large muscles turned
out to have mutations in the gene encoding myostatin (Figure 18−45).
Cancers are similarly the products of mutations that set cells free from
the normal “social” controls operating on cell survival, growth, and proliferation.
Because cancer cells are generally less dependent than normal
cells on signals from other cells, they can out-survive, outgrow, and outdivide
their normal neighbors, producing tumors that can kill their host
(see Chapter 20).
In our discussions of cell division, we have focused entirely on the ordinary
divisions that produce two daughter cells, each with a full and
identical complement of the parent cell’s genetic material. There is, however,
a different and highly specialized type of cell division called meiosis,
which is required for sexual reproduction in eukaryotes. In the next chapter,
we describe the special features of meiosis and how they underlie the
genetic principles that define the laws of inheritance.
activated PI 3-kinase
inhibition of
protein
degradation
activated Akt
activated Tor
stimulation
of protein
synthesis
CELL GROWTH
ECB5 e16.39/18.43
Figure 18−44 The cells in an animal can differ greatly in size.
The neuron and liver cell shown here are drawn at the same scale. A
neuron grows progressively larger after it has terminally differentiated
and permanently stopped dividing. (Neuron adapted from S. Ramón y
Cajal, Histologie du Système Nerveux de l’Homme et de Vertébrés,
1909–1911. Paris: Maloine; reprinted, Madrid: C.S.I.C., 1972.)
neuron
25 µm
liver cell