Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 223

5.3.5.14 Desmin

Desmin, a muscle-specific intermediate filament protein, links the costameres to
the Z disc. It is a component of the intercalated disc in cardiomyocytes. Desmin
interacts with nebulin, spectrin, ankyrins, calpain-3, and the intermediate filament
proteins synemin and syncoilin.

5.3.5.15 Integrins

Integrins couple the cytoskeleton, especially costameres, to the extracellular matrix.
Integrins also link to other cell adhesion-associated signaling proteins and operate
as mechanotransducers. Prolonged mechanical loading of the myocardium causes
maladaptive hypertrophy as well as changes in expression of integrin and extracel-
lular matrix proteins. Mechanical stress applied to integrins elevates cytoskeletal
stiffness.
Sarcolemmal α 2 -integrins, expressed in the embryonic heart, can be

re-expressed in an adult heart bearing unusual mechanical loading. Integrin-

α 1 -and

β 1D
is specific to cardiomyocytes and skeletal myocytes. Integrins associate with focal
adhesion kinase, integrin-linked kinase and its partner affixin, calreticulin, and
melusin.
Cardiomyocytes synthesize at least 4 integrin types:

α 1 β 1 -, α 3 β 1 -, α 5 β 1 -, and

α 7 β 1 -integrins. Integrins- α 5 β 1 interact with extracellular fibronectin.

This interaction is modulated by the contractile state of cardiomyocytes [ 388 ].

α 3 β 1 and -

5.3.5.16 Melusin

Muscle-specific melusin, or integrin- β 1 BP2 (encoded by the

ITGB1BP2 gene), is expressed in skeletal and cardiac, but not smooth myocytes.
It localizes to costameres in the vicinity of Z disc. It senses mechanical stresses.
It promotes the phosphorylation (inactivation) of glycogen synthase kinase GSK3

β 1 -binding protein Itg

β ,

thereby preventing transcription factor activity [ 389 ].

5.3.5.17 Some Types of Sarcomeric Enzymes

Protein Kinase-C

Protein kinase-C , located at the Z disc, regulates cardiomyocyte contractility and

hypertrophy. Activated by GPCRs, PKC binds anchoring proteins, receptors for

activated C-kinases (RACKs). PKC induces normal growth (with preservation

of the cardiomyocyte contractility and without fibrosis), rather than maladaptive
hypertrophy.