Index
We speak of a large rod-shaped cytoskeletal protein.
In 1868, Duchenne de Boulogne clinically described a progressive disease responsible for a muscular dystrophy that today bears his name, without understanding its origin.
On this muscular dystrophy he made it possible to identify the gene and the resulting protein was then called: dystrophin.
Structure of dystrophin
Dystrophin is a protein that is associated with a complex transmembrane of skeletal muscle cells and constitutes 0.01% of the total muscle protein and 5% of the sarcolemic cytoskeleton proteins.
Dystrophin was found to be associated with the plasma membrane both by subcellular fractionation studies and by immunostaining of muscle biopsy cryosections.
Immunoelectron microscopy studies showed that dystrophin was on the intracellular face of the plasma membrane, with a certain periodicity suggesting a network.
Dystrophin is related to the membrane through a series of proteins associated with it.
Dystrophin binds to filamentous actin at multiple sites throughout the molecule, with the strongest interaction sites in the amino-terminal actin-binding domain of the protein.
By linking the intracellular actin network to the plasma membrane and the extracellular basal lamina, the dystrophin-based membrane cytoskeleton likely protects the membrane from contraction-induced damage.
Both sarcoglycans and dystroglycans show secondary reductions in protein levels in patients with dystrophinopathy.
Mutations in any of the four sarcoglycan genes cause autosomal recessive dystrophies that are clinically similar to Duchenne muscular dystrophy.
Function
The dystrophin complex stabilizes the plasma membrane of striated muscle cells.
Loss-of-function mutations in genes encoding dystrophin, or associated proteins, trigger plasma membrane instability and myofiber loss.
Mutations in dystrophin have been extensively cataloged, providing a remarkable structure-function correlation between predicted protein structure and clinical outcomes.
The restoration of dystrophin is probably more complex, due to the role of the dystrophin complex as a broad integrator of the cytoskeleton.
Location of dystrophin
Dystrophin is located in the internal aspect of the sarcolemma and is abundant in the myotendinous junction and in the postsynaptic membrane of the neuromuscular junction.
Dystrophin is an integral part of the cytoskeleton of a muscle and connects the contractile apparatus with the sarcolemma.
Dystrophin is expressed primarily in skeletal, cardiac, and smooth muscle cells, with smaller amounts expressed in the brain and retina.
The isoforms of dystrophin, which are smaller in size, are expressed in almost all tissues examined.
Dystrophin in the brain is important in maintaining the synapse; deficiency of the brain isoform of dystrophin is associated with cognitive deficits seen in patients with dystrophin mutations.
Deletions or abnormalities of the dystrophin gene cause an absence or deficiency of dystrophin, resulting in X-linked Duchenne and Becker muscular dystrophies.
Consequences of a dystrophin disorder
Whether it is a total absence or a partial deficiency (protein truncated and / or in decreased quantity) in dystrophin, the consequences are revealed in various ways.
For skeletal muscle, the integrity of the membrane of the muscle fibers responsible for muscular dystrophy is lost.
In cardiac muscle, abnormal expression of dystrophin is responsible for cardiomyopathy isolated or, in most cases, associated with muscular dystrophy.
In addition, it should be noted that there are cardiomyopathies related to the absence of dystrophin both in patients with Duchenne muscular dystrophy.
To a lesser extent, dystrophin deficiency in smooth muscle can lead to vascular and digestive consequences.
Dystrophin is also present in 5 different isoforms in the central nervous system and 2 isoforms in the retina.
Mutations in the dystrophin gene are responsible for the majority of patients with more or less severe cognitive and / or neuropsychiatric disorders, depending on the number of isoforms affected.
In the retina, the abnormal expression of dystrophin is essentially responsible for an alteration of the electroretinogram in patients.
These defects are directly related to an alteration of the dystrophin sequence (ranging from the absence to a partial loss of the internal sequence).
These will lead to a more or less serious collapse of the organization that normally forms the macromolecular complex, around dystrophin.
On the other hand, the absence of dystrophin alters several intracellular signaling pathways in the skeletal muscle fiber with consequent adverse effects of calcium ions, reactive oxygen species and nitric oxide, which each contribute to the development of muscular dystrophy. .
