The dystrophin-associated protein complex, also known as the dystrophin-associated glycoprotein complex is a

multiprotein complex A protein complex or multiprotein complex is a group of two or more associated polypeptide chains. Protein complexes are distinct from multienzyme complexes, in which multiple catalytic domains are found in a single polypeptide chain. Protein c ...

that includes

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 ...

and the dystrophin-associated proteins. It is one of the two protein complexes that make up the

costamere The costamere is a structural-functional component of striated muscle cells which connects the sarcomere of the muscle to the cell membrane (i.e. the sarcolemma).20: 2327-2331 Costameres are sub-sarcolemmal protein assemblies circumferentially a ...

in striated muscle cells. The other complex is the ''integrin-vinculin-talin complex''.

Structure

The dystrophin-associated protein complex includes

. Dystrophin binds to actin of the

cytoskeleton The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...

, and also to proteins in the

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

. The dystrophin-associated protein complex also contains dystrophin-associated proteins. This includes a four subunit

sarcoglycan complex 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 ...

, which is fixed to dystrophin in

muscle cell A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a muscl ...

s. In the epithelia of the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

, dystrophin may be replaced with

utrophin Utrophin is a protein that in humans is encoded by the ''UTRN'' gene. The protein encoded by this gene is a component of the cytoskeleton. Utrophin was found during research into Duchenne's muscular dystrophy. The name is a contraction for ''ubiq ...

Aquaporin 4 Aquaporin-4, also known as AQP-4, is a water channel protein encoded by the ''AQP4'' gene in humans. AQP-4 belongs to the aquaporin family of integral membrane proteins that conduct water through the cell membrane. A limited number of aquaporins a ...

may be connected to the dystrophin-associated protein complex.

Function

The dystrophin-associated protein complex is important for cell structure and

cell signalling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...

. It is one of two protein complexes found in the

in striated muscle fibres.

Clinical significance

Many forms of

muscular dystrophy Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time. The disorders differ as to which muscles are primarily affe ...

are associated with disorders of the dystrophin-associated protein complex. Muscular dystrophy, the result of mutations in the genes that encode for dystrophin and the associated proteins that binds to it can arise in various forms. The most common form is known as

Duchenne muscular dystrophy Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis fol ...

(DMD). DMD is usually discovered in early childhood and is most often seen occurring in males. There are several associated symptoms that can be observed in such patients including but not limited to a delay in walking and sitting, difficulty in breathing and heart failure. These symptoms are found as a result of the inability to synthesize dystrophin and associate protein complexes that leave muscles weak and unable to repair any damaged sustained. These perpetually weak muscles prohibit normal physical activity.

Therapy

There has been extensive research to discover treatment for DMD. The most common drug treated against DMD is known to be Deflazacort yielding the greatest benefits with the most acceptable side effects. Physical therapy consists of varying exercises that aim to increase muscle strength and durability so to facilitate normal physical activity and is recommended to begin as early as possible after diagnosis. Contracture intervention is recommended for patients in the middle ambulatory stage. However, surgical approach to DMD is declining as less invasive treatment becomes available. While treatment for DMD has been observed to improve muscle function and quality of life, a cure to the debilitating disease remains to be found.

Therapeutic Microdystrophin

*Delandistrogene Moxeparvovec - Systemic Gene Transfer with rAAVrh74.MHCK7.micro-dystrophin.

References

Protein complexes {{biochem-stub