The costamere is a structural-functional component of

striated muscle Striated muscle tissue is a muscle tissue that features repeating functional units called sarcomeres. Under the microscope, sarcomeres are visible along muscle fibers, giving a striated appearance to the tissue. The two types of striated muscle a ...

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 striated muscle, Skeletal muscles are composed of tubular ...

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 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 Skeletal muscle#Skeletal muscle cells, muscle fibers, and these cells contain ...

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 fibre or a cardiomyocyte. It consists of a lipid bilayer and a thin ...

in striated muscle cells and are thus considered one of several "

Achilles' heel An Achilles' heel (or Achilles heel) is a weakness despite overall strength, which can lead to downfall. While the mythological origin refers to a physical vulnerability, idiomatic references to other attributes or qualities that can lead to do ...

s" 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. ''Myopathy'' means muscle disease (Greek language, Greek : myo- ''muscle'' + patheia ''pathos, -pathy'' : ''suffering''). This meaning implies t ...

. 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 (DGC or DAGC), contains various integral and peripheral membrane proteins such as dystroglycans 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 Collagen () is the main structural protein in the extracellular matrix of the connective tissues of many animals. It is the most abundant protein in mammals, making up 25% to 35% of protein content. Amino acids are bound together to form a trip ...

and

laminin Laminins are a family of glycoproteins of the extracellular matrix of all animals. They are major constituents of the basement membrane, namely the basal lamina (the protein network foundation for most cells and organs). Laminins are vital to bi ...

). Therefore, it is one of the features of the sarcolemma which helps to couple the

to the extracellular connective tissue as some experiments have shown. Desmin 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 sarcoglycans 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 costa ...

, the sarcoglycans (including alpha, beta, gamma, and lambda sarcoglycan),

sarcospan Sarcospan is a protein that in humans is encoded by the SSPN gene. Originally identified as Kirsten ras associated gene (KRAG), sarcospan is a 25-kDa transmembrane protein located in the dystrophin-associated protein complex of skeletal muscle ce ...

, dystroglycan (alpha and beta), and syntrophin. 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

extracellular matrix In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and bio ...

. 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 extracellular matrix. 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