Essential Cell Biology 5th edition

Muscle Contraction
605
(A)
actin
10 nm
troponin
complex
tropomyosin
tropomyosin
blocking
myosinbinding
site
end-on view
of actin filament
(B)
+ Ca 2+
– Ca 2+
myosin-binding
site exposed by
Ca 2+ -mediated
tropomyosin
movement
proteins is tropomyosin, a rigid, rod-shaped molecule that binds in the
groove of the actin helix, where it prevents the myosin heads from associating
with the actin filament. The other is troponin, a protein complex
that includes a Ca 2+ -sensitive protein associated with the end of a tropomyosin
molecule. When the concentration of Ca 2+ in the cytosol rises,
Ca 2+ binds to troponin and induces a change ECB5 e17.46-17.46 in its shape. This in turn
causes the tropomyosin molecules to shift their positions slightly, allowing
myosin heads to bind to the actin filaments, initiating contraction
(Figure 17–46B).
Because the signal from the plasma membrane is passed within milliseconds
(via the T tubules and sarcoplasmic reticulum) to every sarcomere
in the cell, all the myofibrils in the cell contract at the same time. The
increase in Ca 2+ in the cytosol is transient because, when the nerve signal
terminates, the Ca 2+ is rapidly pumped back into the sarcoplasmic reticulum
by abundant Ca 2+ pumps in its membrane (discussed in Chapter 12).
As soon as the Ca 2+ concentration returns to the resting level, troponin
and tropomyosin molecules move back to their original positions. This
reconfiguration once again blocks myosin binding to actin filaments,
thereby ending the contraction.
Different Types of Muscle Cells Perform Different
Functions
The highly specialized contractile machinery in muscle cells is thought
to have evolved from the simpler contractile bundles of myosin and actin
filaments found in all eukaryotic cells. The myosin-II in nonmuscle cells
is also activated by a rise in cytosolic Ca 2+ , but the mechanism of activation
is different from that of the muscle-specific myosin-II. An increase in
Ca 2+ leads to the phosphorylation of nonmuscle myosin-II, which alters
the myosin conformation and enables it to interact with actin. A similar
activation mechanism operates in smooth muscle, which is present
in the walls of the stomach, intestine, uterus, and arteries, and in many
other structures that undergo slow and sustained involuntary contractions.
This mode of myosin activation is relatively slow, because time is
needed for enzyme molecules to diffuse to the myosin heads and carry
out the phosphorylation and subsequent dephosphorylation. However,
this mechanism has the advantage that—unlike the mechanism used
by skeletal muscle cells—it can be activated by a variety of extracellular
signals: thus smooth muscle, for example, is triggered to contract by epinephrine,
serotonin, prostaglandins, and several other signal molecules.
In addition to skeletal and smooth muscle, other forms of muscle each
perform a specific mechanical function. Heart—or cardiac—muscle, for
instance, drives the circulation of blood. The heart contracts autonomously
for the entire life of the organism—some 3 billion (3 × 10 9 ) times
in an average human lifetime. Even subtle abnormalities in the actin or
myosin of heart muscle can lead to serious disease. For example, mutations
in the genes that encode cardiac myosin-II or other proteins in the
sarcomere cause familial hypertrophic cardiomyopathy, a hereditary disorder
responsible for sudden death in young athletes.
Figure 17–46 Skeletal muscle contraction
is controlled by tropomyosin and
troponin complexes. (A) An actin filament
in muscle showing the positions of
tropomyosin and troponin complexes along
the filament. Every tropomyosin molecule
has seven evenly spaced regions with a
similar amino acid sequence, each of which
is thought to bind to an actin monomer in
the filament. (B) This cross section of the
muscle actin filament reveals how Ca 2+
binding to the troponin complex (not
shown) leads to movement of tropomyosin
away from the myosin-binding site.
QUESTION 17–10
A. Note that in Figure 17−46,
troponin molecules are evenly
spaced along an actin filament,
with one troponin found every
seventh actin molecule. How do you
suppose troponin molecules can be
positioned this regularly? What does
this tell you about the binding of
troponin to actin filaments?
B. What do you suppose would
happen if you mixed actin
filaments with (i) troponin alone,
(ii) tropomyosin alone, or
(iii) troponin plus tropomyosin, and
then added myosin? Would the
effects be dependent on Ca 2+ ?