Dystrophin

Dystrophin is a rod-shaped is_associated_with::cytoplasmic is_associated_with::protein, and a vital part of a is_associated_with::protein complex that connects the is_associated_with::cytoskeleton of a is_associated_with::muscle fiber to the surrounding is_associated_with::extracellular matrix through the is_associated_with::cell membrane. This complex is variously known as the is_associated_with::costamere or the is_associated_with::dystrophin-associated protein complex. Many muscle proteins, such as α-is_associated_with::dystrobrevin, is_associated_with::syncoilin, is_associated_with::synemin, is_associated_with::sarcoglycan, is_associated_with::dystroglycan, and is_associated_with::sarcospan, colocalize with dystrophin at the costamere.

The dystrophin gene is one of the longest human genes known, covering 2.5 is_associated_with::megabases (0.08% of the human genome) at locus Xp21. The is_associated_with::primary transcript measures about 2,400 is_associated_with::kilobases and takes 16 hours to transcribe; the mature is_associated_with::mRNA measures 14.0 kilobases. The 79 is_associated_with::exons code for a protein of over 3500 amino acid residues.

Function
Dystrophin is a protein located between the is_associated_with::sarcolemma and the outermost layer of is_associated_with::myofilaments in the muscle fiber (is_associated_with::myofiber). It is a cohesive protein, linking is_associated_with::actin filaments to another support protein that resides on the inside surface of each muscle fiber’s plasma membrane (sarcolemma). This support protein on the inside surface of the sarcolemma in turn links to two other consecutive proteins for a total of three linking proteins. The final linking protein is attached to the fibrous is_associated_with::endomysium of the entire muscle fiber. Dystrophin supports muscle fiber strength, and the absence of dystrophin reduces muscle stiffness, increases sarcolemmal deformability, and compromises the mechanical stability of costameres and their connections to nearby myofibrils; as shown in recent studies where biomechanical properties of the sarcolemma and its links through costameres to the contractile apparatus were measured, and helps to prevent muscle fiber injury. Movement of thin filaments (actin) creates a pulling force on the extracellular connective tissue that eventually becomes the tendon of the muscle.

Pathology
Dystrophin deficiency has been definitively established as one of the root causes of the general class of myopathies collectively referred to as is_associated_with::muscular dystrophy. The large is_associated_with::cytosolic protein was first identified in 1987 by is_associated_with::Louis M. Kunkel, after the 1986 discovery of the mutated gene that causes is_associated_with::Duchenne muscular dystrophy (DMD).

Normal skeletal muscle tissue contains only small amounts of dystrophin (about 0.002% of total muscle protein), but its absence (or abnormal expression) leads to the development of a severe and currently incurable constellation of symptoms most readily characterized by several aberrant intracellular signaling pathways that ultimately yield pronounced myofiber is_associated_with::necrosis as well as progressive muscle weakness and fatigability. Most DMD patients become wheelchair-dependent early in life, and the gradual development of cardiac hypertrophy&mdash;a result of severe myocardial fibrosis&mdash;typically results in premature death in the first two or three decades of life. is_associated_with::Mutations in the dystrophin gene that lead to the production of less defective, but still only partially functional dystrophin protein, result in a display of a much milder dystrophic phenotype in affected patients, resulting in the disease known as is_associated_with::Becker's muscular dystrophy (BMD). In some cases the patient's phenotype is such that experts may decide differently on whether a patient should be diagnosed with DMD or BMD. The theory currently most commonly used to predict whether a mutation will result in a DMD or BMD phenotype, is the reading frame rule.

Though its role in airway smooth muscle is not well established, recent research indicates that dystrophin along with other subunits of dystrophin glycoprotein complex is associated with phenotype maturation.

Interactions
Dystrophin has been shown to interact with:
 * is_associated_with::DTNA,
 * SNTA1,  and
 * is_associated_with::SNTB1.

Neanderthal admixture
A variant of the dysmorphin gene, which is on the is_associated_with::X chromosome, named B2006, appears to be an is_associated_with::introgression from a is_associated_with::Neanderthal-modern human mating.

Other sources

 * Saladin, Kenneth. Anatomy and Physiology: The Unity of Form and Function, 6th ed. McGraw-Hill. New York, 2012.
 * "DMD." Genetics Home Reference. U.S. National Library of Medicine, 2 Dec. 2012. Web. 09 Dec. 2012.