Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 212

5.3.3.2 Myofibrils Scaffolding

Costamere

Myofibrils are held in position by scaffolds of desmin filaments, anchored by
costameres , the cortical parts of the cytoskeleton, enriched in vinculin 35 along the
sarcolemma (Fig. 5.8 ). The costameres maintain the spatial structure of sarcomeres
and couple the cardiomyocytes to the extracellular matrix. The membrane skeleton
is made from spectrin and dystrophin , adapting the sarcolemma to CMC functioning
and contributing to the force transmission. The costameres, membrane skeleton, and
cytoskeleton are linked to the extracellular matrix by integral membrane proteins
such as integrins, dystrophin-glycoprotein complexes and β -dystroglycan-laminin

bounds. Dystrophin and -dystroglycan are membrane proteins that are distributed

in the sarcolemma and T tubules.

β

Myosin-Binding Protein-C: Actin-Myosin Connector and Speed Reducer

The cardiac isoform of myosin-binding protein-C MyBPc3, a thick filament-
associated sarcomeric protein member of the immunoglobulin superclass, is located
in C zone of A bands.
Cardiac MyBPc binds to actin, myosin, and titin filaments, thereby participating
in the organization of the sarcomere structure. Modulator MyBPc3 of sarcomere
contractility stabilizes actin in its filamentous state, links actin and myosin filaments,
and modulates actin-myosin interaction [ 368 ].
Protein MyBPc occupies a portion of the overlap zone — C zone. It reversibly
binds via its C-terminus to the myosin filament. Its N-terminus reversibly links to the
actin filament, thereby creating a secondary actomyosin connection. It contributes
to regulating contraction velocity [ 369 ].
The MyBPc3 N-terminus slows actomyosin motion in parts of the thick filament
within the C zone. The cardiac isoform contains a domain adjacent to its N-terminus
endowed with several serine residues. Contraction slowing is tuned by phosphory-
lation of 4 serines (Ser273, Ser282, Ser302, and Ser307) [ 369 ]. Dephosphorylation
of MyBPc3 can lead to its proteolytic cleavage.
Phosphorylations of accessory protein MyBPc3 at different sites by Ca 2 + -
calmodulin-activated kinases and protein kinases PKA and PKC maintain thick
filament spacing [ 370 ]. has a charge

distribution with 3 prominent rings of negative potential [ 371 ]. Charge interac-
tions can regulate cardiomyocyte activity via myosin-binding protein-C bound to
S2 [ 372 ].

β -Myosin-2 flexible coiled-coil segment S2 δ

35 Vinculin is also observed in intercalated discs, T tubule membrane, and adherens junctions,
between the myofibrils and sarcolemma.