Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

920 Chapter 16: The Cytoskeleton
Z disc
Z disc
CapZ
titin
tropomodulin
M line
myosin (thick filament)
plus end
of actin
filament
nebulin
minus end
actin (thin filament)
Opposing pairs of an even longer template protein, called titin, position the
thick filaments midway between the Z discs. Titin acts as a molecular spring, with
a long series of immunoglobulin-like domains that can unfold one by one as stress
is applied to the protein. A springlike unfolding and refolding of these domains
keeps the thick filaments poised in the middle of MBoC6 the sarcomere m16.76/16.34 and allows the
muscle fiber to recover after being overstretched. In C. elegans, whose sarcomeres
are longer than those in vertebrates, titin is longer as well, suggesting that it serves
also as a molecular ruler, determining in this case the overall length of each sarcomere.
A Sudden Rise in Cytosolic Ca 2+ Concentration Initiates Muscle
Contraction
The force-generating molecular interaction between myosin thick filaments and
actin thin filaments takes place only when a signal passes to the skeletal muscle
from the nerve that stimulates it. Immediately upon arrival of the signal, the muscle
cell needs to be able to contract very rapidly, with all the sarcomeres shortening
simultaneously. Two major features of the muscle cell make extremely rapid
contraction possible. First, as previously discussed, the individual myosin motor
heads in each thick filament spend only a small fraction of the ATP cycle time
bound to the filament and actively generating force, so many myosin heads can
act in rapid succession on the same thin filament without interfering with one
another. Second, a specialized membrane system relays the incoming signal rapidly
throughout the entire cell. The signal from the nerve triggers an action potential
in the muscle cell plasma membrane (discussed in Chapter 11), and this electrical
excitation spreads swiftly into a series of membranous folds—the transverse
tubules, or T tubules—that extend inward from the plasma membrane around
each myofibril. The signal is then relayed across a small gap to the sarcoplasmic
reticulum, an adjacent weblike sheath of modified endoplasmic reticulum that
surrounds each myofibril like a net stocking (Figure 16–35A and B).
When the incoming action potential activates a Ca 2+ channel in the T-tubule
membrane, Ca 2+ influx triggers the opening of Ca 2+ -release channels in the sarcoplasmic
reticulum (Figure 16–35C). Ca 2+ flooding into the cytosol then initiates
the contraction of each myofibril. Because the signal from the muscle cell plasma
membrane is passed within milliseconds (via the T tubules and sarcoplasmic
reticulum) to every sarcomere in the cell, all of the myofibrils in the cell contract
at once. The increase in Ca 2+ concentration is transient because the Ca 2+ is rapidly
pumped back into the sarcoplasmic reticulum by an abundant, ATP-dependent
Ca 2+ -pump (also called a Ca 2+ -ATPase) in its membrane (see Figure 11–13). Typically,
the cytoplasmic Ca 2+ concentration is restored to resting levels within 30
msec, allowing the myofibrils to relax. Thus, muscle contraction depends on two
processes that consume enormous amounts of ATP: filament sliding, driven by
the ATPase of the myosin motor domain, and Ca 2+ pumping, driven by the Ca 2+ -
pump.
Figure 16–34 Organization of accessory
proteins in a sarcomere. Each giant titin
molecule extends from the Z disc to the
M line—a distance of over 1 μm. Part of
each titin molecule is closely associated
with a myosin thick filament (which
switches polarity at the M line); the rest of
the titin molecule is elastic and changes
length as the sarcomere contracts and
relaxes. Each nebulin molecule is exactly
the length of a thin filament. The actin
filaments are also coated with tropomyosin
and troponin (not shown; see Figure
16–36) and are capped at both ends.
Tropomodulin caps the minus end of the
actin filaments, and CapZ anchors the
plus end at the Z disc, which also contains
α-actinin (not shown).