Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 213

collagen−4

laminin

laminin

dystroglycan

melusin
talin
Vinc

dystrophin

cytoskeletal actin

actinin

MLP

sarcomeric actin

myosin

titin

Tcap MLP Tcap

Z disc M line

Fig. 5.8 Costamere is the junctional structure connecting the sarcomere to the sarcolemma
and extracellular space. Costameres contain 3 main proteic complexes: (1) focal adhesions,
(2) spectrin-based complex, and (3) dystrophin-associated complex. Costameric complexes, like
the proteic complex of Z disc, contain -Actinin

binds directly or indirectly vinculin (Vinc), talin, and melusin (a possible stretch sensor that
links the costamere to integrins), among other proteins.

α -actinin and muscle LIM protein (MLP). α

α -Actinin is thus connected to the

sarcoplasmic domain of muscle-specific 1D -integrin (I). Integrin extracellular domain links to

laminin. The costamere hence coordinates the deformation of the sarcomere, sarcolemma, and
extracellular medium (telethonin). In addition, dystrophin binds actin as well as the dystrophin-
associated protein complex of the sarcolemma and sarcoplasma (dystrobrevin, dystroglycans,
sarcoglycans, sarcospan, and syntrophins). Integral membrane proteins interact with components
of the extracellular matrix via α / β -dystroglycan- α 2-laminin complexes. Therefore, dystrophin
also connects the sarcomere to the sarcolemma and extracellular matrix. Focal adhesions are
composed of sarcoplasmic proteins (i.e., paxillin, talin, tensin, vinculin, and zyxin) that connect
with cytoskeletal actin filaments and transmembrane proteins ( α -and β -dystroglycans, α -, β -, γ -,
and δ -sarcoglycans, dystrobrevin, and syntrophin).

β

Adrenergic stimulation of the myocardium leads to quick phosphorylation of
the cardiac isoform of myosin-binding protein-C by protein kinase-A, as well
as to phosphorylation of troponin-I and phospholamban. These phosphorylations
contribute to the positive inotropic effect of adrenergic substances. Phosphorylation
of MyBPc3 decreases during ischemia-reperfusion injury and pathological hyper-
trophy (Vol. 6 - Chap. 7. Heart Pathologies), reducing the binding quality between
actin and myosin.