Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 222

5.3.5.10 Calsarcins

Calsarcins are calcium-calmodulin-dependent phosphatases, PP3-associated
sarcomeric proteins that are involved in cardiac hypertrophy. Calsarcin-1 is
exclusively expressed by the adult myocardium and slow-twitch skeletal muscle,
calsarcin-2, 62

and calsarcin-3 by fast-twitch skeletal muscle fibers. Calsarcins

interact with α -actinin, telethonin, filamin-2, cypher, and myotilin.

5.3.5.11 PP3 Phosphatase

Phosphatase PP3, or calcineurin, a calcium-calmodulin heterodimer, interacts
with calsarcin-1 at the Z disc. It induces myocardial hypertrophy (Sect. 5.8 ).
It dephosphorylates transcription factors of the NFAT family for translocation into
the nucleus. Cytoplasmic PP3-dependent NFATs can be detected at the Z disc. After
dephosphorylation by PP3, nuclear translocation of NFAT3 allows coactivation of
muscle-specific adenylosuccinate synthetase AdSS1 gene [ 387 ]. 63 Electrical pacing
of cultured cardiomyocytes that serves as a model of cardiac hypertrophy activates
muscle-specific Adss1 gene, but represses non-muscle Adss2 gene.

5.3.5.12 ARGBP2

Ubiquitous Abelson-related gene product (ARG)-binding protein-2 forms a
complex with CBL ubiquitin ligase, a regulator of the actin cytoskeleton and
apoptosis. 64 Agent ArgBP2 associates with and is a substrate of cytosolic Tyr
kinases of the Abelson family Abl1 and Abl2 (or ARG).
Protein ArgBP2 abounds in cardiomyocytes, where it localizes to Z discs of
sarcomeres. This adaptor assembles signaling complexes at Z discs. In particular,
ARG-binding protein-2 binds to -actinin at Z discs. It influences the contractile or

elastic properties of cardiac sarcomeres.

α

5.3.5.13 Calpains

Calcium-dependent cysteine peptidases, calpains, target sarcomeric proteins and
focal adhesions during cell migration. Calpain-3, the isoform specific to striated
muscle, is located at the Z discs, costameres with desmin and ezrin, the M line,
and the I band. Calpain-3 activates NF

κ

B.

62 Calsarcin-2 is also designated as myozenin or FATZ.
63 Cardiac transcription factor GATA4 is also required for Adss1 gene transcription. Electrical
pacing activates the pp3-NFAT3 and GATA4 pathways.
64 Abelson-related gene product is a non-receptor Tyr kinase of the Abelson family (Abl2).