Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

II. Specialization of the Sarcolemma and Sarcoplasm for Muscular Contraction
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but different species of 1/alkali light chains (AI and A2),
which disassociate at a high pH corresponding to essential
light chains ( Lowey et al. , 1969 ; Sweeney and Houdusse,
2004 ; Weeds, 1969 ).
The myosin molecule is composed of head, neck, and
tail domains. Proteolytic digestion with trypsin results in
the formation of two fragments: (1) heavy meromyosin
(HMM), which is composed of the two globular heads of
myosin and a short neck domain composed of the initial
segment of the fibrous portion; and (2) light meromyosin
(LMM), the tail domain composed of the remaining long
fibrous portion. The HMM fragments correspond structurally
to the cross-bridges, whereas the LMM fragments
comprise the bulk of the thick filaments ( Fig. 15-3 ). The
actin-binding capacity, ATP-binding capacity, and actinactivated
ATPase activity of myosin reside in the globular
head. The actin-activated ATPase activity of myosin
appears to reside primarily in the heavy chains and is
greatly boosted by interaction of the heads with myosin
( Sweeney and Houdusse, 2004 ).
b . Thin Myofilaments and Actin
The thin filaments are composed of two F-actin strands
arranged in a double helical configuration. The F-actin
strands are polymers of the globular protein G-actin, and
each G-actin monomer possesses a complementary binding
site for the myosin globular head. Upon combining with
myosin, actin activates the ATPase activity of the myosin
globular head ( Huxley et al. , 1983 ).
2 . Regulatory Proteins
Two proteins (tropomyosin and troponin) work in concert
with calcium to regulate muscle contraction. Tropomyosin,
a fibrous protein, is arranged along the length of the thin
filaments, within the grooves of the two F-actin strands.
Troponin is a globular protein complex composed of three
subunits: TN-I (troponin inhibitory component), TN-T
(tropomyosin-binding component), and TN-C (calciumbinding
component). The TN-T component attaches the
complex to tropomyosin at intervals along the thin myofilaments.
With low sarcoplasmic calcium concentrations
(10 7 M), tropomyosin molecules block the myosin-binding
sites on actin, which prevents the interaction of actin
and myosin. At higher concentrations (10 6 M), calcium
ions combine with the TN-C component to initiate a conformational
change in the TN-I component, which results
in the movement of tropomyosin to free the myosin-binding
sites on actin. With the myosin-binding site on actin
exposed, actin and myosin combine and initiate the cyclical
changes associated with that interaction. When calcium
ion concentrations are reduced through uptake of calcium
by SERCA, the process is reversed and the interaction of
actin and myosin is inhibited.
3 . Structural Proteins
The organization of myofilaments within sarcomeres and
the organization of myofibrils are supported by a complex
cytoskeletal network of intermediate filaments ( Wang and
Ramirez-Mitchell, 1983 ). Intermediate filaments, and a
number of accessory proteins that form fine filaments, (1)
maintain the alignment of myofilaments and sarcomeres,
(2) attach and maintain alignment of adjacent myofibrils,
(3) attach the sarcomeres of peripheral myofibrils to
the sarcolemma, and (4) connect terminal sarcomeres
to the sarcolemma at myotendinous junctions. Collectively,
the cytoskeletal filaments maintain the structural and functional
relationships of the myofilaments and transfer the
forces developed by the myofilaments to the sarcolemma.
a . Alignment of Myofilaments, Sarcomeres, and
Myofibrils
Thick myofilaments are attached to Z lines by small filaments
composed of the protein titin ( Labeit et al. , 1997 ;
Maruyama, 1999 ). The titin filaments arise near the M line
within the axes of the thick filaments and span the length
of the thick filament as well as the I-band region to attach
to the Z line. Within the I-band region, the titin filaments
provide an elastic attachment to the Z line, which imparts
a passive elasticity to sarcomeres. Myosin-binding proteins
attach to the thick filaments and titin and appear to serve a
structural role as well as a role in myofibrillogenesis. An
additional protein, nebulin, forms small filaments that run
the length of thin myofilaments and may regulate the length
of thin myofilaments. The M line within the sarcomere stabilizes
the thick filament lattice by linking neighboring filaments
to each other and has an enzymatic role as well. It
is composed of creatine kinase, myomesin, and M protein
( Craig and Padron, 2004 ).
At the periphery of myofibrils, adjacent Z lines within
the same sarcomere are connected by intermediate filaments
of desmin. Also, intermediate filaments of desmin encircle
the circumference of Z lines and appear to form linkages
with Z lines of adjacent myofibrils to aid in the alignment of
sarcomeres in register with adjacent myofibrils.
b . Attachment of Myofilaments to the Sarcolemma
At the periphery of myofibrils adjacent to the sarcolemma
there are riblike attachments (costomeres), which are present
on either side of Z lines ( Franzini-Armstrong and Horowitz,
2004 ; Maruyama, 1999 ). Desmin filaments appear to be
anchored to the sarcolemma by a number of adhesion proteins
such as vinculin. At myotendinous junctions, the
thin myofilaments of the last sarcomere attach to the sarcolemma,
which is thrown into numerous villous projections.
The thin myofilaments are anchored by the proteins
α -actinin and vinculin, among others. Growth in the length
of muscle fibers occurs at the myotendinous junctions by the
addition of new sarcomeres ( Griffin et al. , 1971 ).