epsilon-sarcoglycan replaces alpha-sarcoglycan in smooth muscle to form a unique dystrophin-glycoprotein complex.
The sarcoglycan complex has been well characterized in striated muscle, and defects in its components are associated with muscular dystrophy and cardiomyopathy. Here, we have characterized the smooth muscle sarcoglycan complex. By examination of embryonic muscle lineages and biochemical fractionation studies, we demonstrated that epsilon-sarcoglycan is an integral component of the smooth muscle sarcoglycan complex along with beta- and delta-sarcoglycan. Analysis of genetically defined animal models for muscular dystrophy supported this conclusion. The delta-sarcoglycan-deficient cardiomyopathic hamster and mice deficient in both dystrophin and utrophin showed loss of the smooth muscle sarcoglycan complex, whereas the complex was unaffected in alpha-sarcoglycan null mice in agreement with the finding that alpha-sarcoglycan is not expressed in smooth muscle cells. In the cardiomyopathic hamster, the smooth muscle sarcoglycan complex, containing epsilon-sarcoglycan, was fully restored following intramuscular injection of recombinant delta-sarcoglycan adenovirus. Together, these results demonstrate a tissue-dependent variation in the sarcoglycan complex and show that epsilon-sarcoglycan replaces alpha-sarcoglycan as an integral component of the smooth muscle dystrophin-glycoprotein complex. Our results also suggest a molecular basis for possible differential smooth muscle dysfunction in sarcoglycan-deficient patients.
Straub
V
V
Howard Hughes Medical Institute, Department of Physiology and Biophysics, Department of Neurology, University of Iowa College of Medicine, Iowa City, Iowa 52242, USA.
Ettinger
A J
AJ
Durbeej
M
M
Venzke
D P
DP
Cutshall
S
S
Sanes
J R
JR
Campbell
K P
KP
D000818:Animals; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D004622:Embryo, Mammalian; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D049031:Sarcoglycans
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans