title: gamma-Sarcoglycan deficiency increases cell contractility, apoptosis and MAPK pathway activation but does not affect adhesion.
abstract: The functions of gamma-sarcoglycan (gammaSG) in normal myotubes are largely unknown, however gammaSG is known to assemble into a key membrane complex with dystroglycan and its deficiency is one known cause of limb-girdle muscular dystrophy. Previous findings of apoptosis from gammaSG-deficient mice are extended here to cell culture where apoptosis is seen to increase more than tenfold in gammaSG-deficient myotubes compared with normal cells. The deficient myotubes also exhibit an increased contractile prestress that results in greater shortening and widening when the cells are either lightly detached or self-detached. However, micropipette-forced peeling of single myotubes revealed no significant difference in cell adhesion. Consistent with a more contractile phenotype, acto-myosin striations were more prominent in gammaSG-deficient myotubes than in normal cells. An initial phosphoscreen of more than 12 signaling proteins revealed a number of differences between normal and gammaSG(-/-) muscle, both before and after stretching. MAPK-pathway proteins displayed the largest changes in activation, although significant phosphorylation also appeared for other proteins linked to hypertension. We conclude that gammaSG normally moderates contractile prestress in skeletal muscle, and we propose a role for gammaSG in membrane-based signaling of the effects of prestress and sarcomerogenesis.
authors.affiliation: Pennsylvania Muscle Institute, University of Pennsylvania Medical Center, D-700 Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6083, USA.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Griffin
authors.forename: Huisheng
authors.initials: H
authors.lastname: Feng
authors.forename: Manorama
authors.initials: M
authors.lastname: Tewari
authors.forename: Pedro
authors.initials: P
authors.lastname: Acosta
authors.forename: Masataka
authors.initials: M
authors.lastname: Kawana
authors.forename: H Lee
authors.initials: HL
authors.lastname: Sweeney
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Discher
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D049031:Sarcoglycans / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D049031:Sarcoglycans; D020928:Mitogen-Activated Protein Kinases