Cardiomyocytes - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 218

Titin is connected to the sarcoplasmic reticulum by the giant muscular protein
obscurin and ankyrin . Obscurin also binds to calmodulin in a calcium-independent
fashion. It possesses also binding sites for different isoforms of ankyrin-1 and -
2 from the sarcoplasmic reticulum as well as signaling mediators, in addition to
sarcomeric proteins. In addition, obscurin and ankyrin regulate ryanodine channel
distribution.
Striated muscle preferentially expressed gene product (SPEG) 43 is closely related
to obscurin, with which it shares Ser/Thr kinase MLCK-like domains.
Obscurin helps to keep extrasarcomeric structures in lateral alignment with
the sarcomere during contraction-relaxation cycles. Moreover, obscurin-related
proteins such as obscurin-like protein-1 (ObsL1) serves also as cytoskeletal adaptor.
Protein ObsL1 links the cytoskeleton to the cell membrane, particularly at sites
of between-cell and cell-matrix adhesions [ 383 ]. Multiple isoforms arise from
alternative splicing. Agent ObsL1 localizes to intercalated discs, perinuclear region,
and M and Z lines. This cytoskeletal linker positions and stabilizes intercellular
contacts and organelles within the cytoskeletal framework.
The titin kinase and zinc finger scaffold protein Neighbor of BRCA1 gene
NBR1 44 form a signaling complex at the M band that can recruit the ubiquitin
ligase Tripartite motif-containing protein TriM55 45 Enzyme TriM55 binds to serum
response factor involved in the synthesis of many muscle proteins.

5.3.5.5 Nebulette and Filamin and Its Partners

Nebulin is an actin-binding protein. Nebulette is the cardiac-specific small isoform
of nebulin. Filamin-2 46 is the filamin isoform specific to striated myocyte. Filamin-2
binds to several partners, such as calsarcin, myotilin, sarcoglycan, and β 1 integrin.

-actinin-2, filamin-2, and actin. It also interacts with calsarcin-
1and-2. Myopalladin interacts with manifold proteins, such as nebulette,

Myotilin binds to α

-actinin,
and cardiac ankyrin repeat protein. Myopodin 47 moves from Z discs to the nucleus.

α

43 A.k.a. aortic preferentially expressed protein-1 (APEG1). It is preferentially expressed in
differentiated vascular smooth myocytes. Its production falls during dedifferentiation of vascular
smooth myocytes from a quiescent and contractile to a proliferative and synthetic phenotype, a
feature of atherosclerosis. Subtypes SPEG α and SPEG β can be detected in skeletal and cardiac
myocytes.
44 A.k.a. cell migration-inducing gene-19 protein (MIG19).
45 A.k.a. muscle-specific RING finger MuRF2 and RING finger protein-29 (RNF29).
46 Filamin-2 is also called filamin-C, ABP280, and

γ -filamin.

47 Myopodin is also called synaptopodin-2.