LGMD: The Cellular View

Article Highlights:

This article is part of the In Focus: Limb-Girdle Muscular Dystrophy package, which ran in the October-December 2013 issue of Quest.

In addition to this article, this series contains seven additional sections, links to which can be found at the bottom of this page. These include:

by Margaret Wahl on October 3, 2013 - 9:10am

Quest Vol. 20, No. 4

LGMD cell illustrationEach muscle fiber (mature muscle cell) is surrounded by a membrane (covering) that separates the inside of the fiber from the material outside the fiber. The material outside the fiber is called the extracellular matrix.

Some of the genetic defects that cause limb-girdle muscular dystrophies affect proteins in the membrane, such as the sarcoglycans, or proteins involved in membrane maintenance, such as dysferlin. LGMD2C, 2D, 2E and 2F are caused by sarcoglycan deficiencies, and LGMD2B is caused by a lack of the dysferlin protein.

Some of the genetic defects that cause LGMD affect proteins that are in the extracellular matrix, such as collagen 6 and alpha-dystroglycan. Bethlem myopathy is a form of LGMD that results from abnormalities or a deficiency of collagen 6, and LGMD2P is caused by a deficiency of the alpha-dystroglycan protein.

Other LGMDs arise from a lack of one of the proteins that helps “sugar-coat” alpha-dystroglycan with molecules called glycans (sugars), a process that’s essential for alpha-dystroglycan’s functioning. Deficiencies of the fukutin protein (LGMD2M), of the fukutin-related protein (LGMD2I), of POMT1 (LGMD2K), of POMT2 (LGMD2N), or of POMGnT1 (LGMD2O) are examples of these types of LGMD.

Abnormalities or deficiencies of the proteins desmin and plectin interfere with the functioning of the sarcomeres, the contractile units inside each muscle fiber. Each sarcomere contains string-like proteins that slide past each other during muscle contraction. LGMD1E results from defects in the desmin protein, and LGM2Q from a lack of the plectin protein.

Still other forms of LGMD affect various “command and control” functions of the cell. For instance, abnormalities in lamin A/C — a protein that surrounds each cell nucleus in a muscle fiber — cause LGMD1B, probably by affecting the way the nuclei function. (Muscle fibers contain many nuclei.)

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