Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 214

5.3.4 Z Disc, a Stretch-Sensing Structure

The structure of sarcomeres is highly ordered. Nonetheless, sarcomeres permanently
exchange molecules with surrounding cellular structures. The cytoskeletal support
system surrounds and supports myofibrils.
The Z discs not only serve as crosslinkers of thin filaments and transmitters
of force generated by the myofilaments, but also as stretch receptors and signal
transducers [ 373 ]. Various signaling molecules interact with Z-disc proteins. Several
interacting substances shuttle between the Z disc and other cellular compartments.
The Z discs are mainly composed of

α -actinins assembled in successive layers

(width 20 nm) that provide a skeleton for the insertion of actin filaments, titin,

and nebulin (Fig. 5.9 ). Z discs of neighboring sarcomeres are aligned in parallel and
connected via desmin. The sarcomere is coupled to the sarcolemma by costameres
that comprise peripheral Z-disc molecules and subsarcolemmal proteins. Z disc and
costameric proteins are involved in mechanotransduction.

∼

5.3.5 Main Sarcomeric Constituents

5.3.5.1 α -Actinin

α -Actinin-2 forms homodimers

aligned in an antiparallel fashion. It contains 3 domains: actin-binding sequence,
central rod, and domain with 2 calcium-binding motifs.

- Actinin -2 is the main component of the Z disc. α

-Actinin-2 interacts
with multiple molecules, such as the Rho effector protein Ser/Thr kinase PKN,
phospholipase-D2, 36 and G-protein-coupled receptor kinases. 37

α

-Actinin interacts
with Z-line filamentous actin-capping protein (CapZ). Dimer CapZ is composed of
α

α

and β -subunits.

5.3.5.2 Titin

Titin, the largest human protein, spans the sarcomere from the M line to the Z line,
where it is anchored. Titin serves not only as a structural component, but also as a

36 Phospholipase-D2, mainly located at the sarcolemma, regulates Ca 2 + fluxes. It is inhibited by
α

-actinin and ARF1 [ 374 ].
37 Phospholipase-D2 modulates GRK activity. In the presence of calmodulin and α -actinin, GRK5
phosphorylates soluble, but not plasmalemmal substrates. In the presence of phosphatidylinositol
(4,5)-bisphosphate and

α

-actinin, GRK5 phosphorylates plasmalemmal, but not soluble sub-

strates [ 375 ].