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The costamere is a structural-functional component of
striated muscle Striations means a series of ridges, furrows or linear marks, and is used in several ways: * Glacial striation * Striation (fatigue), in material * Striation (geology), a ''striation'' as a result of a geological fault * Striation Valley, in An ...
cells which connects the
sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...
of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331 Costameres are sub-sarcolemmal protein assemblies circumferentially aligned in register with the
Z-disk A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called musc ...
of peripheral
myofibril A myofibril (also known as a muscle fibril or sarcostyle) is a basic rod-like organelle of a muscle cell. Skeletal muscles are composed of long, tubular cells known as muscle fibers, and these cells contain many chains of myofibrils. Each myo ...
s. They physically couple force-generating sarcomeres with the
sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath) also called the myolemma, is the cell membrane surrounding a skeletal muscle fiber or a cardiomyocyte. It consists of a lipid bilayer and a thin oute ...
in striated muscle cells and are thus considered one of several " Achilles' heels" of skeletal muscle, a critical component of striated muscle morphology which, when compromised, is thought to directly contribute to the development of several distinct
myopathies In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. ''Myopathy'' means muscle disease (Greek : myo- ''muscle'' + patheia '' -pathy'' : ''suffering''). This mean ...
. The
dystrophin-associated protein complex The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up ...
, also referred to as the
dystrophin-associated glycoprotein complex The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a multiprotein complex that includes dystrophin and the dystrophin-associated proteins. It is one of the two protein complexes that make up ...
(DGC or DAGC), contains various integral and peripheral membrane proteins such as
dystroglycans Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene. Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
and sarcoglycans, which are thought to be responsible for linking the internal cytoskeletal system of individual myofibers to structural proteins within the extracellular matrix (such as collagen and
laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major components of the basal lamina (one of the layers of the basement membrane), the protein network foundation for most cells and organs. The laminins ...
). Therefore, it is one of the features of the sarcolemma which helps to couple the
sarcomere A sarcomere (Greek σάρξ ''sarx'' "flesh", μέρος ''meros'' "part") is the smallest functional unit of striated muscle tissue. It is the repeating unit between two Z-lines. Skeletal muscles are composed of tubular muscle cells (called mus ...
to the extracellular connective tissue as some experiments have shown.
Desmin Desmin is a protein that in humans is encoded by the ''DES'' gene. Desmin is a muscle-specific, type III intermediate filament that integrates the sarcolemma, Z disk, and nuclear membrane in sarcomeres and regulates sarcomere architecture. Str ...
protein may also bind to the DAG complex, and regions of it are known to be involved in signaling.


Structure

Costameres are highly complex networks of proteins and glycoproteins, and can be considered as consisting of two major protein complexes: the dystrophin-glycoprotein complex (DGC) and the integrin-vinculin-talin complex. The
sarcoglycan The sarcoglycans are a family of transmembrane proteins (α, β, γ, δ or ε) involved in the protein complex responsible for connecting the muscle fibre cytoskeleton to the extracellular matrix, preventing damage to the muscle fibre sarcolemma t ...
s of the DGC and the integrins of the integrin-vinculin-talin complex attach directly to filamin C, a component of the Z-disk, linking these protein complexes of costameres to complexes of the Z-disk. Restated, filamin C physically links the two complexes that constitute the costamere to sarcomeres by interacting with the sarcoglycans in the DGC and the integrins of the integrin-vinculin-talin complex. The DGC consists of peripheral and integral proteins that physically traverse the sarcolemma and connect the ECM to the F-actin based cytoskeleton. The core proteins of DGC are
dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the cost ...
, the sarcoglycans (including alpha, beta, gamma, and lambda sarcoglycan),
sarcospan Originally identified as Kirsten ras associated gene (krag), Sarcospan (SSPN) is a 25-kDa transmembrane protein located in the dystrophin-associated protein complex of skeletal muscle cells, where it is most abundant. It contains four transmembrane ...
,
dystroglycan Dystroglycan is a protein that in humans is encoded by the ''DAG1'' gene. Dystroglycan is one of the dystrophin-associated glycoproteins, which is encoded by a 5.5 kb transcript in ''Homo sapiens'' on chromosome 3. There are two exons that are s ...
(alpha and beta), and
syntrophin The syntrophins are a family of five 60-kiloDalton proteins that are associated with dystrophin, the protein associated with Duchenne muscular dystrophy and Becker muscular dystrophy. The name comes from the Greek word ''syntrophos'', meaning "comp ...
. These proteins are thought to play an important role in maintaining the structural integrity of sarcolemma during contraction and stretching, and loss of these core proteins results in progressive contraction induced damage. The vinculin and talin components of the integrin-vinculin-talin complex are cytoskeletal proteins physically anchored to the costamere as a whole via the integrin components, which are transmembrane proteins that interact directly with filamin C of the Z disk.


Function

Costameres have several primary functions. First, they keep the sarcolemma in line with the sarcomere during contraction and subsequent relaxation. They are also responsible for the lateral transmission of the sarcomere-generated contractile force to the sarcolemma and the ECM. Only 20-30% of the total force generated by sarcomere contraction is transmitted longitudinally, suggesting that the majority of the force generated by sarcomeres is transduced in the lateral direction, perpendicular to the contracting myofibril fibers. Most of the force generated by the sarcomeres deep inside the muscle fiber is transmitted perpendicularly to adjacent myofibrils until it reaches the peripheral myofibrils. At that point, the costameric complex channels the force through the sarcolemma to the ECM. The lateral transmission of force by costameres helps maintain uniform sarcomere lengths in adjacent muscle cells that are under the control of different motor units and are therefore not synchronized in their active contractions; restated, if one muscle fiber is actively contracting and an adjacent one is not, the lateral force transmission helps this second fiber to shorten as well. Costameres also transmit forces in the opposite direction, transmitting the forces of external mechanical stress from the sarcolemma to the Z-disk. Costameres are also involved in protecting the relatively weak and labile sarcolemma from the mechanical stresses of contraction and stretching. The proteins mechanically support the lipid bilayer, and also may facilitate an organized folding of the plasma membrane ("festooning") that minimizes stress on the bilayer during contraction and stretching. Finally, costameres are also involved in the orchestration of mechanically related signaling.


Pathology

The dysfunction of the proteins involved in costameres contributes to some muscular diseases, including muscular dystrophies and cardiomyopathies.


Dynamics

Costameres are dynamic structures. Several studies have suggested that costameres are responsive to mechanical, electrical, and chemical stimuli. For instance, mechanical tension is critical in regulating costameric protein expression, stability, and organization, and dystrophin deficient costameres may sense increased mechanical stress and attempt to compensate with filament recruitment.


References

{{Authority control Histology