Dystrophin-glycoprotein complex and Ras and Rho GTPase signaling are altered in muscle atrophy.
The dystrophin-glycoprotein complex (DGC) is a sarcolemmal complex whose defects cause muscular dystrophies. The normal function of this complex is not clear. We have proposed that this is a signal transduction complex, signaling normal interactions with matrix laminin, and that the response is normal growth and homeostasis. If so, the complex and its signaling should be altered in other physiological states such as atrophy. The amount of some of the DGC proteins, including dystrophin, beta-dystroglycan, and alpha-sarcoglycan, is reduced significantly in rat skeletal muscle atrophy induced by tenotomy. Furthermore, H-Ras, RhoA, and Cdc42 decrease in expression levels and activities in muscle atrophy. When the small GTPases were assayed after laminin or beta-dystroglycan depletion, H-Ras, Rac1, and Cdc42 activities were reduced, suggesting a physical linkage between the DGC and the GTPases. Dominant-negative Cdc42, introduced with a retroviral vector, resulted in fibers that appeared atrophic. These data support a putative role for the DGC in transduction of mechanical signals in muscle.
Chockalingam
Priya Sethu
PS
Department of Molecular Sciences, University of Tennessee Health Sciences Center, Memphis, Tennessee 38163, USA.
Cholera
Rushina
R
Oak
Shilpa A
SA
Zheng
Yi
Y
Jarrett
Harry W
HW
Thomason
Donald B
DB
D000818:Animals; D003598:Cytoskeletal Proteins / Q000378:metabolism; D049030:Dystroglycans; D016189:Dystrophin / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000502:physiology; D006023:Glycoproteins / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism; D009133:Muscular Atrophy / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D049031:Sarcoglycans; D015398:Signal Transduction / Q000502:physiology*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D018631:ras Proteins / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D006023:Glycoproteins; D007797:Laminin; D008562:Membrane Glycoproteins; D049031:Sarcoglycans; D049030:Dystroglycans; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D018631:ras Proteins; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein