Muscle and Nonmuscle Contractile Systems
or absent, leading to frequent pneumonia, colds, and ear
infections. These defects were originally described in con-
junction with situs inversus (lateral transposition of the
thoracic and abdominal viscera). Some embryonic cells
have a single flagellum that is presumed to be important
for movement to their proper location. The flagellar defect
may make the cells unable to migrate properly, giving rise
to situs inversus. Only about half of persons with immotile
cilia have situs inversus, suggesting that chirality (handed-
ness) of embryonic organization is random in the absence
of flagellar function. Association of the three abnormali-
ties (bronchiectasis, sinusitis, situs inversus) is known as
Kartagener’s syndrome.
These defects also cause infer-
tility in males because the sperm are immotile. Affected
females have nearly normal fertility despite the probable
lack of ciliary activity in the oviducts. The function of
microtubules other than in cilia and flagella is presumed
to be normal; otherwise cell division could not occur.
are another large family of motor proteins.
Thirteen have been described altogether, 11 in mouse
brain. How many occur in humans is uncertain. Cytosolic
kinesin is a tetramer of two heavy chains of unit M.W.
124,000 and two light chains of unit M.W. 64,000. The
heavy chains have a head region and a tail, similar to
myosin except that the tail is largely globular rather than a
rod. There are structural similarities between myosin and
kinesin heads, and in key functional groups, such as the
helices flanking the ATPase site, the sequence homology
is high. The light chains are associated with the tail. Typ-
ically, kinesin is a (+)-directed motor, i.e., it tries to pull
whatever it is attached to toward the (+) end of the micro-
tubule. In an axon, that would be away from the cell body.
Cytosolic dynein, which is smaller and simpler than ax-
onemal dynein, is a (—)-directed motor. In most kinesins,
the motor region is at the N-terminal half of the molecule,
but in some it is in the C-terminal region. Most of these
latter kinesins are, like dynein, (—)-directed.
Kinesin has in common with cytosolic dynein and trans-
port myosins (e.g., myosin I) a property called
This is the term used to refer to the fact that a single
motor molecule, when dragging a vesicle or other cargo
along a filament or a microtubule, cannot let go of that fila-
ment or microtubule lest the motor and its cargo drift away
or continually reattach to the same site. Instead the motor
must remain bound to one G-actin or tubulin while “reach-
ing for” the next one. A similar argument applies to other
motor proteins, such as DNA helicase which crawls along
DNA unzipping the strands, and the ribosomal motors
which pull the RNA and the nascent polypeptide through
the ribosome. In contrast, myosins whose functional form
is filaments, such as myosin II, need not exhibit this prop-
erty: any given myosin molecule need not be attached to
the actin filament because attachment and orientation of
the myosin filament to the actin filament will be main-
tained so long as one or two myosins anywhere in the
filament remain attached. Which features of these motor
molecules determine the presence or absence of proces-
sivity remains a mystery.
Supplemental Readings and References
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L. A. Amos and R. A. Cross: Structure and dynamics of molecular motors.
C u rren t O p in io n in S tru ctu ra l B io lo g y
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G. Bonne, L. Carrier, P. Richard, B. Hainque, and K. Schwartz: Familial
hypertrophic cardiomyopathy: from mutations to functional defects.
C ir-
cu la tio n R esearch
580 (1998).
R. Cooke: Actomyosin interaction in striated muscle.
P h ysio lo g ica l R eview s
77,671 (1997).
M. A. Geeves and K. C. Holmes: Structural mechanism of muscle contrac-
A n n u a l R eview o f B io ch em istry
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A. M. Gordon, E. Honsher, and M. Regnier: Regulation of contraction in
striated muscle.
P h ysio lo g ica l R eview s
853 (2000).
N. Hirokawa: Kinesin and dynein superfamily proteins and the mechanism
of organelle transport.
S c ie n ce
519 (1998).
A. Horowitz, C. B. Menice, R. Laporte, and K. G. Morgan: Mechanisms of
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H. Lodish, D. Baltimore, A. Berk, et al.: Microfilaments: Cell motility and
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M o lecu la r C ell B iology.
H. Lodish
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W. H. Freeman, New York, 1995, p. 991.
G. J. Lutz and R. L. Lieber: Skeletal muscle myosin II structure and function.
E xercise S p o rt S cien ce R eview
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L. A. Sabourin and M. A. Rudnicki: The molecular regulation of myogenesis.
C lin ic a l G en etics
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S. Sach, F. J. Kull, and E. Mandelkow: Motor proteins of the kinesin family.
Structures, variations, and nucleotide binding sites.
E uropean Jo u rn a l o f
B io ch em istry
262, 1
S. Schiaffino and C. Reggiani: Molecular diversity of myofibrillar proteins:
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C. A. Sewry: Immunocytochemical analysis of human muscular dystrophy.
M icrosc. Res. Tech.
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J. M. Squire and E. P. Morris: A new look at thin filament regulation in
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F A SE B J o u rn a l
761 (1998).
M. J. Tanasijevic, C. P. Canon, and E. M. Antman: The role of cardiac
troponin-I (CTnl) in risk stratification of patients with unstable coronary
artery disease.
C lin ica l C a rd io lo g y
22, 11
R. H. Wade and A. A. Hyman: Microtubule structure and dynamics.
C urrent
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D. C. Wallace: Mitochondrial DNA in aging and disease.
S cien tific A m erica n
A. Weiss and L. A. Leinwand: The mammalian myosin heavy chain gene
A n n u a l R eview o f C ell D evo p m en ta l B io lo g y
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