DYSTROPHIN IN VOLUNTARY MUSCLES
Many excellent research studies in the past 10 years have shown precisely where dystrophin is located in muscle cells and have shed much light on what this protein does.
Cross-section view of a muscle, which is made up of bundles of fibers. Dystrophin is located just under the membrane that surrounds each muscle fiber. |
In the cells of voluntary muscles (those we can move at will, such as the arm and leg and back muscles), dystrophin is located just under the cell membrane, a thin sheath that surrounds muscle cells. Voluntary muscles are also known as striated muscles, because of their microscopic appearance, and skeletal muscles, because most of them are attached to bones.
Mature muscle cells are called muscle fibers, because they're actually made from what were once several immature muscle cells, now fused into one long fiber. Voluntary muscle fibers are long and thin, and most of them move bones when they contract. They have to exert a lot of force without tearing or being damaged in the process.
Dystrophin, lying just under the fiber membrane, attaches to a small cluster of other muscle proteins that actually span the membrane and attach to tissue outside the fiber, which is called the extracellular matrix.
In the last few years, other forms of muscular dystrophy, such as limb-girdle muscular dystrophy and one type of congenital muscular dystrophy, have been traced to defects in other proteins in the cluster.
Along the muscle fiber membrane, a cluster of proteins appears repeatedly. Dystrophin attaches to that cluster. Various forms of muscular dystrophy occur when one or more of these proteins fails to work properly. (Illustration adapted from one by Volker Straub, University of Iowa, Current Opinion in Neurology, April 1997) |
Research suggests that dystrophin plays a vital role in preventing damage to the membrane during muscle fiber contraction, although the details of how it does this aren't very clear. Damage to the membrane of any cell is a major problem. Leaky membranes allow substances that can kill a cell to leak in and substances vital to a cell's health to leak out. In DMD, it isn't completely clear which process is more important, but most researchers believe that leaks in the fiber membrane are at the root of muscle degeneration in this disorder. (In muscular dystrophies, as muscle fibers degenerate, or die off, they're replaced by useless scarlike tissue.)
Some recent research suggests that dystrophin may have other functions in addition to its role in preserving the structure of the membrane. It may also carry signals from one part of the fiber to another -- for example, from the periphery to the interior of the fiber. If this is true, the loss of this kind of signal may also play a role in muscle degeneration.
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