Dystrophin predominantly localizes to the transverse tubule/Z-line regions of single ventricular myocytes and exhibits distinct associations with the membrane.
Dystrophin is a high molecular weight protein present at low abundance in skeletal, cardiac and smooth muscle and in trace amounts in brain. In skeletal muscle, dystrophin is uniformly distributed along the inner surface of the plasma membrane. Biochemical fractionation studies have shown that all detectable skeletal muscle dystrophin is tightly associated with a complex of wheat germ agglutinin (WGA)-binding and concanavalin A (Con A) binding sarcolemmal glycoproteins. Absence of dystrophin is the primary biochemical defect in patients with Duchenne muscular dystrophy and leads to segmental necrosis of their skeletal myofibers. Although present in similar amounts in normal cardiac and skeletal muscle, the absence of dystrophin from cardiac muscle has less severe effects on the survival of cardiac cells. We have therefore examined whether there are differences in the properties of cardiac and skeletal dystrophin. We report that in contrast to skeletal muscle, cardiac dystrophin is distributed between distinct pools: a soluble cytoplasmic pool, a membrane-bound pool not associated with WGA-binding glycoproteins and a membrane-bound pool associated with WGA-binding glycoproteins. Cardiac dystrophin was not associated with any Con A binding glycoproteins. Immunohistochemical localization studies in isolated ventricular myocytes reveal a distinct punctate staining pattern for dystrophin, approximating to the level of the transverse tubule/Z-line and contrasting with the uniform sarcolemmal staining reported for skeletal muscle fibers. The distinct properties of cardiac dystrophin suggest unique roles for this protein in cardiac versus skeletal muscle function.
Peri
V
V
Department of Pharmacology, University of Ottawa, Ontario, Canada.
Ajdukovic
B
B
Holland
P
P
Tuana
B S
BS
D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D002462:Cell Membrane / Q000737:chemistry*; D003429:Cross Reactions; D003600:Cytosol / Q000737:chemistry; D016189:Dystrophin / Q000032:analysis* / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D006023:Glycoproteins / Q000032:analysis; D006352:Heart Ventricles; D051379:Mice; D018101:Mice, Inbred mdx; D008969:Molecular Sequence Data; D009132:Muscles / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry* / Q000166:cytology; D011817:Rabbits; D012508:Sarcolemma / Q000737:chemistry; D012518:Sarcomeres / Q000737:chemistry*; D012519:Sarcoplasmic Reticulum / Q000737:chemistry; D013552:Swine
D016189:Dystrophin; D006023:Glycoproteins